T cell immunity or tolerance as a consequence of self antigen presentation.
In this study we investigated the basis for immunity or tolerance to a mouse serum protein, the fifth component of complement (C5). In C5-deficient mice this protein is absent from serum and therefore they are not tolerized. Immunization of C5-deficient mice with C5-sufficient serum generates CD4+ T cells, which recognize C5 presented in the context of class II. No C5-specific responses were observed in T cells from C5-sufficient mice. We show that this self protein is processed and presented with class II by cells from C5-sufficient tolerant mice and can be recognized by C5-specific T cell clones and hybrids in the absence of exogenously added antigen. The stimulation of C5-specific T cells by C5-sufficient antigen-presenting cells is not a consequence of C5 secretion and subsequent processing in vitro but rather employs C5 peptide/class II complexes generated in vivo. We conclude that this self antigen is presented in normal mice in a form recognizable by T cells to induce and maintain immunological tolerance.
Basel Institute for Immunology, Switzerland.
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Stockinger
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D002478:Cells, Cultured; D003182:Complement C5 / Q000008:administration & dosage / Q000172:deficiency; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008806:Mice, Inbred AKR; D008808:Mice, Inbred CBA; D010455:Peptides / Q000276:immunology; D010641:Phenotype; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
D003182:Complement C5; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D010455:Peptides