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Kai W. Wucherpfennig, MD, PhD


Studies: Novel Strategies for Cancer Immunotherapy

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Researcher

  • Chair, Cancer Immunology and Virology, Dana-Farber Cancer Institute
  • Director, Center for Cancer Immunotherapy Research, Dana-Farber Cancer Institute
  • Professor of Neurology, Brigham and Women's Hospital and Harvard Medical School
  • Associate Member, Broad Institute of MIT and Harvard

Contact Information

  • Office Phone Number617-632-3086
  • Fax617-582-9164

Bio

Dr. Wucherpfennig received his MD in 1986 and his PhD in 1987 from the University of Goettingen, Germany. He completed research fellowships at Brigham and Women's Hospital and the Department of Molecular and Cellular Biology, Harvard University. In 1995, he joined DFCI, where he is principally involved in basic laboratory research that focuses on T cell immunology and the role of T cells in cancer immunology. 

Recent Awards:

  • Harry Weaver Neuroscience Scholar, National Multiple Sclerosis Society 1992
  • Langheinrich Prize, University of Berlin 1995
  • Elected as Member Henry Kunkel Society, Rockefeller University 2007
  • Elected as Member of American Society for Clinical Investigation 2006
  • Elected as Fellow, American Society for the Advancement of Science 2009
  • 800x600 Transformative RO1, NIH Director's Transformative Research Award Program 2012

Research

Innovative Research in T cell Biology and Cancer Immunology

T cells have the unique capacity to specifically detect and selectively destroy cancer cells based on T cell receptor-driven recognition of tumor antigens. All therapeutic approaches that have shown efficacy in the clinic are fundamentally based on enhancing the function of cytotoxic T cells. The Wucherpfennig lab aims to develop the next generation of cancer immunotherapies by in-depth mechanistic studies that identify the critical molecular switches controlling the ability of T cells to destroy cancers in highly immunosuppressive tumor microenvironments.

We recently reported a novel in vivo approach that enables discovery of negative regulators of T cell function in tumors. The genes we discovered provide exciting opportunities to mechanistically understand key regulatory mechanisms in T cells. Furthermore, they provide an opportunity to enhance the anti-tumor activity of adoptive T cell therapies, for example with T cells that express a chimeric antigen receptor (CAR).

We have also developed novel approaches to investigate immune responses in patients responding to cancer immunotherapies. A subset of patients generates antibodies against immunosuppressive molecules, and we developed a technique for isolation of memory B cells that produce such antibodies. A single cell PCR procedure provides the sequences of the antibody heavy and light chain genes, enabling production of recombinant antibodies for in depth mechanistic studies. We have found that such patient-derived antibodies can have intriguing functional properties and strong anti-tumor activity in humanized mouse models. This approach thereby enables us to directly learn from patients who respond to cancer immunotherapies and to develop human therapeutic antibodies.

Interactions between cancer cells and immune cells drive transitions to mesenchymal-like states in glioblastoma. Cancer Cell. 2021 May 25.
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cIAP1/2 antagonism eliminates MHC class I-negative tumors through T cell-dependent reprogramming of mononuclear phagocytes. Sci Transl Med. 2021 May 19; 13(594).
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Inhibition of CDK4/6 promotes CD8 T-cell memory formation. Cancer Discov. 2021 May 03.
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CARM1 Inhibition Enables Immunotherapy of Resistant Tumors by Dual Action on Tumor cells and T cells. Cancer Discov. 2021 Mar 11.
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Understanding and treating the inflammatory adverse events of cancer immunotherapy. Cell. 2021 Mar 18; 184(6):1575-1588.
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Multimodal pooled Perturb-CITE-seq screens in patient models define mechanisms of cancer immune evasion. Nat Genet. 2021 03; 53(3):332-341.
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Inhibitory CD161 receptor identified in glioma-infiltrating T cells by single-cell analysis. Cell. 2021 Mar 04; 184(5):1281-1298.e26.
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Immunosuppressive Myeloid Cells Induce Nitric Oxide-Dependent DNA Damage and p53 Pathway Activation in CD8+ T Cells. Cancer Immunol Res. 2021 Apr; 9(4):470-485.
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Opposing immune and genetic mechanisms shape oncogenic programs in synovial sarcoma. Nat Med. 2021 02; 27(2):289-300.
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Personal neoantigen vaccines induce persistent memory T cell responses and epitope spreading in patients with melanoma. Nat Med. 2021 03; 27(3):515-525.
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Integrin avß6-TGFß-SOX4 Pathway Drives Immune Evasion in Triple-Negative Breast Cancer. Cancer Cell. 2021 Jan 11; 39(1):54-67.e9.
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Mechanism of EBV inducing anti-tumour immunity and its therapeutic use. Nature. 2021 02; 590(7844):157-162.
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Neoadjuvant Nivolumab or Nivolumab Plus Ipilimumab in Untreated Oral Cavity Squamous Cell Carcinoma: A Phase 2 Open-Label Randomized Clinical Trial. JAMA Oncol. 2020 10 01; 6(10):1563-1570.
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Inhibition of MAN2A1 Enhances the Immune Response to Anti-PD-L1 in Human Tumors. Clin Cancer Res. 2020 11 15; 26(22):5990-6002.
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Single-Cell RNA-Seq Reveals Cellular Hierarchies and Impaired Developmental Trajectories in Pediatric Ependymoma. Cancer Cell. 2020 07 13; 38(1):44-59.e9.
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Correction: Hdac3 is an epigenetic inhibitor of the cytotoxicity program in CD8 T cells. J Exp Med. 2020 07 06; 217(7).
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Hdac3 is an epigenetic inhibitor of the cytotoxicity program in CD8 T cells. J Exp Med. 2020 07 06; 217(7).
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Molecular Pathways of Colon Inflammation Induced by Cancer Immunotherapy. Cell. 2020 08 06; 182(3):655-671.e22.
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Metabolic labeling and targeted modulation of dendritic cells. Nat Mater. 2020 11; 19(11):1244-1252.
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Synthetic Lethal and Resistance Interactions with BET Bromodomain Inhibitors in Triple-Negative Breast Cancer. Mol Cell. 2020 06 18; 78(6):1096-1113.e8.
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Acquired resistance to combined BET and CDK4/6 inhibition in triple-negative breast cancer. Nat Commun. 2020 05 11; 11(1):2350.
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Inhibition of MICA and MICB Shedding Elicits NK-Cell-Mediated Immunity against Tumors Resistant to Cytotoxic T Cells. Cancer Immunol Res. 2020 06; 8(6):769-780.
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Distinct Mesenchymal Cell Populations Generate the Essential Intestinal BMP Signaling Gradient. Cell Stem Cell. 2020 03 05; 26(3):391-402.e5.
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Ascl2-Dependent Cell Dedifferentiation Drives Regeneration of Ablated Intestinal Stem Cells. Cell Stem Cell. 2020 03 05; 26(3):377-390.e6.
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Replicational Dilution of H3K27me3 in Mammalian Cells and the Role of Poised Promoters. Mol Cell. 2020 04 02; 78(1):141-151.e5.
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Inhibition of Haspin Kinase Promotes Cell-Intrinsic and Extrinsic Antitumor Activity. Cancer Res. 2020 02 15; 80(4):798-810.
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Discovery of specialized NK cell populations infiltrating human melanoma metastases. JCI Insight. 2019 12 05; 4(23).
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MHC-II neoantigens shape tumour immunity and response to immunotherapy. Nature. 2019 10; 574(7780):696-701.
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T-Scan: A Genome-wide Method for the Systematic Discovery of T Cell Epitopes. Cell. 2019 08 08; 178(4):1016-1028.e13.
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Subclonal cooperation drives metastasis by modulating local and systemic immune microenvironments. Nat Cell Biol. 2019 07; 21(7):879-888.
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Publisher Correction: Landscape of B cell immunity and related immune evasion in human cancers. Nat Genet. 2019 Jun; 51(6):1068.
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Visualization and quantification of NK cell-mediated cytotoxicity over extended time periods by image cytometry. J Immunol Methods. 2019 06; 469:47-51.
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Epithelial endoplasmic reticulum stress orchestrates a protective IgA response. Science. 2019 03 01; 363(6430):993-998.
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Landscape of B cell immunity and related immune evasion in human cancers. Nat Genet. 2019 03; 51(3):560-567.
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Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial. Nature. 2019 01; 565(7738):234-239.
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Radiotherapy induces responses of lung cancer to CTLA-4 blockade. Nat Med. 2018 12; 24(12):1845-1851.
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A Cancer Cell Program Promotes T Cell Exclusion and Resistance to Checkpoint Blockade. Cell. 2018 11 01; 175(4):984-997.e24.
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FAP Delineates Heterogeneous and Functionally Divergent Stromal Cells in Immune-Excluded Breast Tumors. Cancer Immunol Res. 2018 12; 6(12):1472-1485.
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Rapid CLIP dissociation from MHC II promotes an unusual antigen presentation pathway in autoimmunity. J Exp Med. 2018 10 01; 215(10):2617-2635.
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Signatures of T cell dysfunction and exclusion predict cancer immunotherapy response. Nat Med. 2018 10; 24(10):1550-1558.
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Engineered MBP-specific human Tregs ameliorate MOG-induced EAE through IL-2-triggered inhibition of effector T cells. J Autoimmun. 2018 08; 92:77-86.
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Vaccine-elicited receptor-binding site antibodies neutralize two New World hemorrhagic fever arenaviruses. Nat Commun. 2018 05 14; 9(1):1884.
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Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq. Science. 2018 04 20; 360(6386):331-335.
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Antibody-mediated inhibition of MICA and MICB shedding promotes NK cell-driven tumor immunity. Science. 2018 Mar 30; 359(6383):1537-1542.
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Corrigendum: An immunogenic personal neoantigen vaccine for patients with melanoma. Nature. 2018 03 14; 555(7696):402.
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A facile approach to enhance antigen response for personalized cancer vaccination. Nat Mater. 2018 06; 17(6):528-534.
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Signaling by the Epstein-Barr virus LMP1 protein induces potent cytotoxic CD4+ and CD8+ T cell responses. Proc Natl Acad Sci U S A. 2018 01 23; 115(4):E686-E695.
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A major chromatin regulator determines resistance of tumor cells to T cell-mediated killing. Science. 2018 02 16; 359(6377):770-775.
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T cell-targeting nanoparticles focus delivery of immunotherapy to improve antitumor immunity. Nat Commun. 2017 11 23; 8(1):1747.
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Immunotherapy for glioblastoma: on the sidelines or in the game? Discov Med. 2017 11; 24(133):201-208.
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Erratum: The microRNA miR-31 inhibits CD8+ T cell function in chronic viral infection. Nat Immunol. 2017 09 19; 18(10):1173.
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Immunomodulation for glioblastoma. Curr Opin Neurol. 2017 06; 30(3):361-369.
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The microRNA miR-31 inhibits CD8+ T cell function in chronic viral infection. Nat Immunol. 2017 Jul; 18(7):791-799.
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Noninvasive Imaging of Human Immune Responses in a Human Xenograft Model of Graft-Versus-Host Disease. J Nucl Med. 2017 06; 58(6):1003-1008.
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Multicomponent Injectable Hydrogels for Antigen-Specific Tolerogenic Immune Modulation. Adv Healthc Mater. 2017 Mar; 6(6).
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Studying Dynamic Plasma Membrane Binding of TCR-CD3 Chains During Immunological Synapse Formation Using Donor-Quenching FRET and FLIM-FRET. Methods Mol Biol. 2017; 1584:259-289.
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Cytotoxic T Cells in PD-L1-Positive Malignant Pleural Mesotheliomas Are Counterbalanced by Distinct Immunosuppressive Factors. Cancer Immunol Res. 2016 12; 4(12):1038-1048.
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Binding of the cytoplasmic domain of CD28 to the plasma membrane inhibits Lck recruitment and signaling. Sci Signal. 2016 07 26; 9(438):ra75.
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Genetic screens to study the immune system in cancer. Curr Opin Immunol. 2016 08; 41:55-61.
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Clinical and MRI phenotype of children with MOG antibodies. Mult Scler. 2016 Feb; 22(2):174-84.
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Molecular mechanisms for contribution of MHC molecules to autoimmune diseases. Curr Opin Immunol. 2014 Dec; 31:24-30.
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Immunotherapy advances for glioblastoma. Neuro Oncol. 2014 Nov; 16(11):1441-58.
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B cell homeostasis and follicle confines are governed by fibroblastic reticular cells. Nat Immunol. 2014 Oct; 15(10):973-81.
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Membrane association of the CD3e signaling domain is required for optimal T cell development and function. J Immunol. 2014 Jul 01; 193(1):258-67.
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Abnormal B cell memory subsets dominate HIV-specific responses in infected individuals. J Clin Invest. 2014 Jul; 124(7):3252-62.
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Deconstructing the peptide-MHC specificity of T cell recognition. Cell. 2014 May 22; 157(5):1073-87.
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Discovering cancer immunotherapy targets in vivo. Oncoimmunology. 2014; 3:e28500.
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The tumor microenvironment shapes lineage, transcriptional, and functional diversity of infiltrating myeloid cells. Cancer Immunol Res. 2014 Jul; 2(7):655-67.
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Polarized release of T-cell-receptor-enriched microvesicles at the immunological synapse. Nature. 2014 Mar 06; 507(7490):118-23.
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In vivo discovery of immunotherapy targets in the tumour microenvironment. Nature. 2014 Feb 06; 506(7486):52-7.
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Mechanisms of peptide repertoire selection by HLA-DM. Trends Immunol. 2013 Oct; 34(10):495-501.
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Cracking the code of human T-cell immunity. Nat Biotechnol. 2013 Jul; 31(7):609-10.
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An update on vaccine therapy and other immunotherapeutic approaches for glioblastoma. Expert Rev Vaccines. 2013 Jun; 12(6):597-615.
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Crossreactivity of a human autoimmune TCR is dominated by a single TCR loop. Nat Commun. 2013; 4:2623.
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Crystal structure of the HLA-DM-HLA-DR1 complex defines mechanisms for rapid peptide selection. Cell. 2012 Dec 21; 151(7):1557-68.
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Local changes in lipid environment of TCR microclusters regulate membrane binding by the CD3e cytoplasmic domain. J Exp Med. 2012 Dec 17; 209(13):2423-39.
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Identification of HIV-1-specific regulatory T-cells using HLA class II tetramers. AIDS. 2012 Oct 23; 26(16):2112-5.
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Functional single-cell analysis of T-cell activation by supported lipid bilayer-tethered ligands on arrays of nanowells. Lab Chip. 2013 Jan 07; 13(1):90-9.
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Alternative RISC assembly: binding and repression of microRNA-mRNA duplexes by human Ago proteins. RNA. 2012 Nov; 18(11):2041-55.
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Podoplanin-rich stromal networks induce dendritic cell motility via activation of the C-type lectin receptor CLEC-2. Immunity. 2012 Aug 24; 37(2):276-89.
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Self-reactive human CD4 T cell clones form unusual immunological synapses. J Exp Med. 2012 Feb 13; 209(2):335-52.
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Th17 cells induce ectopic lymphoid follicles in central nervous system tissue inflammation. Immunity. 2011 Dec 23; 35(6):986-96.
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The mechanism of HLA-DM induced peptide exchange in the MHC class II antigen presentation pathway. Curr Opin Immunol. 2012 Feb; 24(1):105-11.
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Autoimmune diseases have been the focus of intense research efforts. Curr Opin Immunol. 2011 Dec; 23(6):699-701.
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Cell surface display of functional human MHC class II proteins: yeast display versus insect cell display. Protein Eng Des Sel. 2011 Sep; 24(9):701-9.
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Ex vivo characterization and isolation of rare memory B cells with antigen tetramers. Blood. 2011 Jul 14; 118(2):348-57.
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T cell receptor recognition of self and foreign antigens in the induction of autoimmunity. Semin Immunol. 2011 Apr; 23(2):84-91.
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Impaired thymic tolerance to a-myosin directs autoimmunity to the heart in mice and humans. J Clin Invest. 2011 Apr; 121(4):1561-73.
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MicroRNA expression profiling identifies activated B cell status in chronic lymphocytic leukemia cells. PLoS One. 2011 Mar 08; 6(3):e16956.
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A highly tilted binding mode by a self-reactive T cell receptor results in altered engagement of peptide and MHC. J Exp Med. 2011 Jan 17; 208(1):91-102.
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HLA-DM captures partially empty HLA-DR molecules for catalyzed removal of peptide. Nat Immunol. 2011 Jan; 12(1):54-61.
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The first structures of T cell receptors bound to peptide-MHC. J Immunol. 2010 Dec 01; 185(11):6391-3.
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The structural basis for intramembrane assembly of an activating immunoreceptor complex. Nat Immunol. 2010 Nov; 11(11):1023-9.
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Response multilayered control of T cell receptor phosphorylation. Cell. 2010 Sep 03; 142(5):669-71.
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Targeted regulation of self-peptide presentation prevents type I diabetes in mice without disrupting general immunocompetence. J Clin Invest. 2010 Apr; 120(4):1324-36.
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Structural biology of the T-cell receptor: insights into receptor assembly, ligand recognition, and initiation of signaling. Cold Spring Harb Perspect Biol. 2010 Apr; 2(4):a005140.
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Positively selecting peptides: their job does not end in the thymus. Nat Immunol. 2009 Nov; 10(11):1143-4.
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Structural alterations in peptide-MHC recognition by self-reactive T cell receptors. Curr Opin Immunol. 2009 Dec; 21(6):590-5.
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Age-dependent B cell autoimmunity to a myelin surface antigen in pediatric multiple sclerosis. J Immunol. 2009 Sep 15; 183(6):4067-76.
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In vivo enhancement of peptide display by MHC class II molecules with small molecule catalysts of peptide exchange. J Immunol. 2009 May 15; 182(10):6342-52.
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Suppression of autoimmune diabetes by soluble galectin-1. J Immunol. 2009 Mar 01; 182(5):2641-53.
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Regulation of T cell receptor activation by dynamic membrane binding of the CD3epsilon cytoplasmic tyrosine-based motif. Cell. 2008 Nov 14; 135(4):702-13.
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Variable patterns of programmed death-1 expression on fully functional memory T cells after spontaneous resolution of hepatitis C virus infection. J Virol. 2008 May; 82(10):5109-14.
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Induction of antigen-specific regulatory T cells in wild-type mice: visualization and targets of suppression. Proc Natl Acad Sci U S A. 2008 Mar 04; 105(9):3479-84.
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B cells and autoantibodies in the pathogenesis of multiple sclerosis and related inflammatory demyelinating diseases. Adv Immunol. 2008; 98:121-49.
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Ex vivo analysis of human T lymphotropic virus type 1-specific CD4+ cells by use of a major histocompatibility complex class II tetramer composed of a neurological disease-susceptibility allele and its immunodominant peptide. J Infect Dis. 2007 Dec 15; 196(12):1761-72.
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Common themes in the assembly and architecture of activating immune receptors. Nat Rev Immunol. 2007 Nov; 7(11):841-50.
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Empty class II major histocompatibility complex created by peptide photolysis establishes the role of DM in peptide association. J Biol Chem. 2007 Jul 20; 282(29):21425-36.
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Dominant-negative effect of the heterozygous C104R TACI mutation in common variable immunodeficiency (CVID). J Clin Invest. 2007 Jun; 117(6):1550-7.
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Regulation of activated CD4+ T cells by NK cells via the Qa-1-NKG2A inhibitory pathway. Immunity. 2007 May; 26(5):593-604.
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Polyspecificity of T cell and B cell receptor recognition. Semin Immunol. 2007 Aug; 19(4):216-24.
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Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation. Nat Med. 2007 Apr; 13(4):423-31.
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Structural basis of T-cell specificity and activation by the bacterial superantigen TSST-1. EMBO J. 2007 Feb 21; 26(4):1187-97.
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Self-antigen tetramers discriminate between myelin autoantibodies to native or denatured protein. Nat Med. 2007 Feb; 13(2):211-7.
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The structure of the zetazeta transmembrane dimer reveals features essential for its assembly with the T cell receptor. Cell. 2006 Oct 20; 127(2):355-68.
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A membrane-proximal tetracysteine motif contributes to assembly of CD3deltaepsilon and CD3gammaepsilon dimers with the T cell receptor. J Biol Chem. 2006 Dec 01; 281(48):36977-84.
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Transient immunological control during acute hepatitis C virus infection: ex vivo analysis of helper T-cell responses. J Viral Hepat. 2006 Oct; 13(10):708-14.
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The assembly of diverse immune receptors is focused on a polar membrane-embedded interaction site. PLoS Biol. 2006 May; 4(5):e142.
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Small molecules that enhance the catalytic efficiency of HLA-DM. J Immunol. 2006 Apr 01; 176(7):4208-20.
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Expansion and contraction of HIV-specific CD4 T cells with short bursts of viremia, but physical loss of the majority of these cells with sustained viral replication. J Immunol. 2005 Nov 15; 175(10):6948-58.
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Cutting edge: CD4+CD25+ regulatory T cells contribute to gender differences in susceptibility to experimental autoimmune encephalomyelitis. J Immunol. 2005 Nov 01; 175(9):5591-5.
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Unusual features of self-peptide/MHC binding by autoimmune T cell receptors. Immunity. 2005 Oct; 23(4):351-60.
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Antibodies from inflamed central nervous system tissue recognize myelin oligodendrocyte glycoprotein. J Immunol. 2005 Aug 01; 175(3):1974-82.
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The activating NKG2D receptor assembles in the membrane with two signaling dimers into a hexameric structure. Proc Natl Acad Sci U S A. 2005 May 24; 102(21):7641-6.
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Unconventional topology of self peptide-major histocompatibility complex binding by a human autoimmune T cell receptor. Nat Immunol. 2005 May; 6(5):490-6.
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Convergence on a distinctive assembly mechanism by unrelated families of activating immune receptors. Immunity. 2005 Apr; 22(4):427-38.
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The structural interactions between T cell receptors and MHC-peptide complexes place physical limits on self-nonself discrimination. Curr Top Microbiol Immunol. 2005; 296:19-37.
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The T cell receptor: critical role of the membrane environment in receptor assembly and function. Annu Rev Immunol. 2005; 23:101-25.
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The solvent-inaccessible Cys67 residue of HLA-B27 contributes to T cell recognition of HLA-B27/peptide complexes. J Immunol. 2004 Dec 01; 173(11):6564-73.
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Measuring T cell immunity to influenza vaccination in children after haemopoietic stem cell transplantation. Br J Haematol. 2004 Nov; 127(3):322-5.
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Myelin proteolipid protein-specific CD4+CD25+ regulatory cells mediate genetic resistance to experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A. 2004 Oct 26; 101(43):15434-9.
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Self-peptides that bind with low affinity to the diabetes-associated I-A(g7) molecule readily induce T cell tolerance in non-obese diabetic mice. Eur J Immunol. 2004 Oct; 34(10):2656-63.
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Prevention of type 1 diabetes by gene therapy. J Clin Invest. 2004 Oct; 114(7):969-78.
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Cross-reactive TCR responses to self antigens presented by different MHC class II molecules. J Immunol. 2004 Aug 01; 173(3):1689-98.
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Expression of the B7.1 costimulatory molecule on pancreatic beta cells abrogates the requirement for CD4 T cells in the development of type 1 diabetes. J Immunol. 2004 Jul 15; 173(2):787-96.
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Stoichiometry of the T-cell receptor-CD3 complex and key intermediates assembled in the endoplasmic reticulum. EMBO J. 2004 Jun 16; 23(12):2348-57.
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Suppression of autoimmune disease after vaccination with autoreactive T cells that express Qa-1 peptide complexes. J Clin Invest. 2004 Apr; 113(8):1218-24.
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Molecular mechanisms for the assembly of the T cell receptor-CD3 complex. Mol Immunol. 2004 Apr; 40(18):1295-305.
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A spontaneous model for autoimmune myocarditis using the human MHC molecule HLA-DQ8. J Immunol. 2004 Feb 15; 172(4):2651-8.
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T cell receptor crossreactivity as a general property of T cell recognition. Mol Immunol. 2004 Feb; 40(14-15):1009-17.
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Presentation of a self-peptide in two distinct conformations by a disease-associated HLA-B27 subtype. J Exp Med. 2004 Jan 19; 199(2):151-4.
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Detailed analysis of the effects of Glu/Lys beta69 human leukocyte antigen-DP polymorphism on peptide-binding specificity. Tissue Antigens. 2003 Dec; 62(6):459-71.
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MHC-linked susceptibility to type 1 diabetes: a structural perspective. Ann N Y Acad Sci. 2003 Nov; 1005:119-27.
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Ex vivo analysis of thymic CD4 T cells in nonobese diabetic mice with tetramers generated from I-A(g7)/class II-associated invariant chain peptide precursors. J Immunol. 2003 Oct 15; 171(8):4175-86.
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Ex vivo analysis of human memory CD4 T cells specific for hepatitis C virus using MHC class II tetramers. J Clin Invest. 2003 Sep; 112(6):831-42.
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The shared tumor-associated antigen cytochrome P450 1B1 is recognized by specific cytotoxic T cells. Blood. 2003 Nov 01; 102(9):3287-94.
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Myelin basic protein-reactive autoantibodies in the serum and cerebrospinal fluid of multiple sclerosis patients are characterized by low-affinity interactions. J Neuroimmunol. 2003 Mar; 136(1-2):140-8.
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Detection of autoreactive myelin proteolipid protein 139-151-specific T cells by using MHC II (IAs) tetramers. J Immunol. 2003 Jan 15; 170(2):870-7.
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The organizing principle in the formation of the T cell receptor-CD3 complex. Cell. 2002 Dec 27; 111(7):967-79.
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Structural factors contributing to DM susceptibility of MHC class II/peptide complexes. J Immunol. 2002 Nov 01; 169(9):5109-17.
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A functional and structural basis for TCR cross-reactivity in multiple sclerosis. Nat Immunol. 2002 Oct; 3(10):940-3.
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Infectious triggers for inflammatory neurological diseases. Nat Med. 2002 May; 8(5):455-7.
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Human primary and memory cytotoxic T lymphocyte responses are efficiently induced by means of CD40-activated B cells as antigen-presenting cells: potential for clinical application. Blood. 2002 May 01; 99(9):3319-25.
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Insights into autoimmunity gained from structural analysis of MHC-peptide complexes. Curr Opin Immunol. 2001 Dec; 13(6):650-6.
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Equivalent induction of telomerase-specific cytotoxic T lymphocytes from tumor-bearing patients and healthy individuals. Cancer Res. 2001 Dec 01; 61(23):8366-70.
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Mechanisms for the induction of autoimmunity by infectious agents. J Clin Invest. 2001 Oct; 108(8):1097-104.
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Conserved CDR3 regions in T-cell receptor (TCR) CD8(+) T cells that recognize the Tax11-19/HLA-A*0201 complex in a subject infected with human T-cell leukemia virus type 1: relationship of T-cell fine specificity and major histocompatibility complex/peptide/TCR crystal structure. J Virol. 2001 Oct; 75(20):9836-43.
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Type 1 diabetes. Nat Immunol. 2001 Sep; 2(9):767-8.
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Analysis of the relationship between viral infection and autoimmune disease. Immunity. 2001 Jul; 15(1):137-47.
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Structure of a human insulin peptide-HLA-DQ8 complex and susceptibility to type 1 diabetes. Nat Immunol. 2001 Jun; 2(6):501-7.
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Structural basis of molecular mimicry. J Autoimmun. 2001 May; 16(3):293-302.
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Anergy induction by dimeric TCR ligands. J Immunol. 2001 Apr 15; 166(8):5279-85.
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Selective activation and expansion of high-affinity CD4+ T cells in resistant mice upon infection with Leishmania major. Immunity. 2000 Dec; 13(6):771-82.
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Binding of conserved islet peptides by human and murine MHC class II molecules associated with susceptibility to type I diabetes. Eur J Immunol. 2000 Sep; 30(9):2497-506.
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Visualization of myelin basic protein (MBP) T cell epitopes in multiple sclerosis lesions using a monoclonal antibody specific for the human histocompatibility leukocyte antigen (HLA)-DR2-MBP 85-99 complex. J Exp Med. 2000 Apr 17; 191(8):1395-412.
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Kinetics of T-cell receptor binding by bivalent HLA-DR. Peptide complexes that activate antigen-specific human T-cells. J Biol Chem. 2000 Jan 07; 275(1):312-21.
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A humanized model for multiple sclerosis using HLA-DR2 and a human T-cell receptor. Nat Genet. 1999 Nov; 23(3):343-7.
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pH-dependent peptide binding properties of the type I diabetes-associated I-Ag7 molecule: rapid release of CLIP at an endosomal pH. J Exp Med. 1999 Jun 07; 189(11):1723-34.
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Peptide recognition by two HLA-A2/Tax11-19-specific T cell clones in relationship to their MHC/peptide/TCR crystal structures. J Immunol. 1999 May 01; 162(9):5389-97.
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Binding motifs of copolymer 1 to multiple sclerosis- and rheumatoid arthritis-associated HLA-DR molecules. J Immunol. 1999 Apr 15; 162(8):4697-704.
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Structural features of autoreactive TCR that determine the degree of degeneracy in peptide recognition. J Immunol. 1999 Jan 01; 162(1):338-44.
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In vivo survival of viral antigen-specific T cells that induce experimental autoimmune encephalomyelitis. J Exp Med. 1998 Nov 02; 188(9):1725-38.
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Crystal structure of HLA-DR2 (DRA*0101, DRB1*1501) complexed with a peptide from human myelin basic protein. J Exp Med. 1998 Oct 19; 188(8):1511-20.
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Expression and crystallization of the complex of HLA-DR2 (DRA, DRB1*1501) and an immunodominant peptide of human myelin basic protein. Proc Natl Acad Sci U S A. 1998 Sep 29; 95(20):11828-33.
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Recombinant soluble human alpha 3 beta 1 integrin: purification, processing, regulation, and specific binding to laminin-5 and invasin in a mutually exclusive manner. Biochemistry. 1998 Aug 04; 37(31):10945-55.
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Effective treatment of models of multiple sclerosis by matrix metalloproteinase inhibitors. Ann Neurol. 1998 Jul; 44(1):35-46.
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Microbial peptides and superantigens in the pathogenesis of autoimmune diseases of the central nervous system. Semin Immunol. 1998 Feb; 10(1):57-67.
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Activation of autoreactive T cells by peptides from human pathogens. Curr Opin Immunol. 1997 Dec; 9(6):831-8.
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Tolerance induction to myelin basic protein by intravenous synthetic peptides containing epitope P85 VVHFFKNIVTP96 in chronic progressive multiple sclerosis. J Neurol Sci. 1997 Nov 06; 152(1):31-8.
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Recognition of the immunodominant myelin basic protein peptide by autoantibodies and HLA-DR2-restricted T cell clones from multiple sclerosis patients. Identity of key contact residues in the B-cell and T-cell epitopes. J Clin Invest. 1997 Sep 01; 100(5):1114-22.
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Expression of recombinant HLA-DR2 molecules. Replacement of the hydrophobic transmembrane region by a leucine zipper dimerization motif allows the assembly and secretion of soluble DR alpha beta heterodimers. J Biol Chem. 1996 Aug 16; 271(33):20156-62.
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Structural basis for major histocompatibility complex (MHC)-linked susceptibility to autoimmunity: charged residues of a single MHC binding pocket confer selective presentation of self-peptides in pemphigus vulgaris. Proc Natl Acad Sci U S A. 1995 Dec 05; 92(25):11935-9.
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Structure of human T-cell receptors specific for an immunodominant myelin basic protein peptide: positioning of T-cell receptors on HLA-DR2/peptide complexes. Proc Natl Acad Sci U S A. 1995 Sep 12; 92(19):8896-900.
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A review of T-cell receptors in multiple sclerosis: clonal expansion and persistence of human T-cells specific for an immunodominant myelin basic protein peptide. Ann N Y Acad Sci. 1995 Jul 07; 756:241-58.
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Selective binding of self peptides to disease-associated major histocompatibility complex (MHC) molecules: a mechanism for MHC-linked susceptibility to human autoimmune diseases. J Exp Med. 1995 May 01; 181(5):1597-601.
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Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein. Cell. 1995 Mar 10; 80(5):695-705.
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Functional three-domain single-chain T-cell receptors. Proc Natl Acad Sci U S A. 1994 Dec 20; 91(26):12654-8.
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Autoimmunity in the central nervous system: mechanisms of antigen presentation and recognition. Clin Immunol Immunopathol. 1994 Sep; 72(3):293-306.
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Clonal expansion and persistence of human T cells specific for an immunodominant myelin basic protein peptide. J Immunol. 1994 Jun 01; 152(11):5581-92.
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Structural requirements for binding of an immunodominant myelin basic protein peptide to DR2 isotypes and for its recognition by human T cell clones. J Exp Med. 1994 Jan 01; 179(1):279-90.
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Human fetal liver gamma/delta T cells predominantly use unusual rearrangements of the T cell receptor delta and gamma loci expressed on both CD4+CD8- and CD4-CD8- gamma/delta T cells. J Exp Med. 1993 Feb 01; 177(2):425-32.
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Characterization of HTLV-I in vivo infected T cell clones. IL-2-independent growth of nontransformed T cells. J Immunol. 1992 May 15; 148(10):3256-63.
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Gamma delta T-cell receptor repertoire in acute multiple sclerosis lesions. Proc Natl Acad Sci U S A. 1992 May 15; 89(10):4588-92.
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T cell receptor V alpha-V beta repertoire and cytokine gene expression in active multiple sclerosis lesions. J Exp Med. 1992 Apr 01; 175(4):993-1002.
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T-cell activation by autologous human T-cell leukemia virus type I-infected T-cell clones. Proc Natl Acad Sci U S A. 1992 Mar 15; 89(6):2110-4.
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The potential of restricted T cell recognition of myelin basic protein epitopes in the therapy of multiple sclerosis. Ann N Y Acad Sci. 1991 Dec 30; 636:251-65.
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Oligoclonal expansion and CD1 recognition by human intestinal intraepithelial lymphocytes. Science. 1991 Sep 20; 253(5026):1411-5.
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T-cell recognition of myelin basic protein. Immunol Today. 1991 Aug; 12(8):277-82.
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[Isolation and characterization of colloidal soluble polysaccharides in raspberry juice]. Z Lebensm Unters Forsch. 1991 Jul; 193(1):1-8.
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Common T-cell receptor V beta usage in oligoclonal T lymphocytes derived from cerebrospinal fluid and blood of patients with multiple sclerosis. Ann Neurol. 1991 Jan; 29(1):33-40.
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Shared human T cell receptor V beta usage to immunodominant regions of myelin basic protein. Science. 1990 May 25; 248(4958):1016-9.
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Immunologic mechanisms in chronic demyelinating diseases of the central and peripheral nervous system. Res Publ Assoc Res Nerv Ment Dis. 1990; 68:105-16.
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Gene activation during experimental allergic encephalomyelitis. Cloning of new cDNAs. Ann N Y Acad Sci. 1988; 540:264-5.
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