Kishida et al. showed that immune-induced TCR-like antibodies (iTabs) – antibodies that are specific to an antigen peptide–MHC-II complex – were produced during helper T cell responses to immunization with various antigens. These iTabs induced antigen-dependent depletion of target cells, blocked TCR recognition of specific peptide–MHC-II complexes, and prevented activation of antigen-specific T cells, but only when the presented peptides contained specific flanking residues. In a mouse model, treatment with iTabs or immunization with a peptide that induced iTabs effectively limited the development of autoimmune encephalomyelitis.
Contributed by Lauren Hitchings
ABSTRACT: Antigen-specific regulation of T cell response is crucial for limiting hyperimmune response. However, the molecular mechanisms governing specific immune regulation remain unclear. In this study, we discover that antibodies specific to the antigen peptide-MHC class II complex are produced during helper T cell responses to various antigens, including hen egg lysozyme and proteolipid protein peptide. These antibodies specifically inhibit T cell receptor (TCR) recognition of MHC class II molecules presenting specific antigen peptide. We term these antibodies 'immune-induced TCR-like antibodies' or iTabs. Immunization with peptides containing flanking residues induces iTabs whereas immunization with peptides lacking flanking residues does not. Furthermore, we show that immunization with iTab-inducible peptide or iTab treatment suppress autoimmune disease development in a mouse model of experimental autoimmune encephalomyelitis. Thus, our findings provide a strategy for suppressing antigen-specific helper T cell responses using specific peptides, potentially controlling autoimmune diseases.
Author Info: (1) Department of Immunochemistry, Research Institute for Microbial Diseases, The University of Osaka, Suita, Osaka, Japan. (2) Biostructural Mechanism Group, RIKEN SPring-8 Center
Author Info: (1) Department of Immunochemistry, Research Institute for Microbial Diseases, The University of Osaka, Suita, Osaka, Japan. (2) Biostructural Mechanism Group, RIKEN SPring-8 Center, Hyogo, Japan. (3) Department of Drug Target Protein Research, Shinshu University School of Medicine, Matsumoto, Nagano, Japan. Department of Structural Biology and Biochemistry, Institute of New Industry Incubation, Institute of Science Tokyo, Tokyo, Japan. (4) Department of Immunochemistry, Research Institute for Microbial Diseases, The University of Osaka, Suita, Osaka, Japan. Laboratory for Innate Immune Systems, Department of Microbiology and Immunology, Graduate School of Medicine, The University of Osaka, Suita, Osaka, Japan. (5) Biostructural Mechanism Group, RIKEN SPring-8 Center, Hyogo, Japan. Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, Miyagi, Japan. (6) Department of Drug Target Protein Research, Shinshu University School of Medicine, Matsumoto, Nagano, Japan. Department of Structural Biology and Biochemistry, Institute of New Industry Incubation, Institute of Science Tokyo, Tokyo, Japan. (7) Department of Immunochemistry, Research Institute for Microbial Diseases, The University of Osaka, Suita, Osaka, Japan. arase@biken.osaka-u.ac.jp. Laboratory of Immunochemistry, WPI Immunology Frontier Research Center, The University of Osaka, Suita, Osaka, Japan. arase@biken.osaka-u.ac.jp. Center for Advanced Modalities and DDS, The University of Osaka, Suita, Osaka, Japan. arase@biken.osaka-u.ac.jp. Center for Infectious Disease Education and Research, The University of Osaka, Suita, Osaka, Japan. arase@biken.osaka-u.ac.jp.
