title: Specific recognition of thymic self-peptides induces the positive selection of cytotoxic T lymphocytes.
abstract: To understand how thymic selection gives rise to T cells that are capable of major histocompatibility complex (MHC)-restricted recognition of antigen but are tolerant of self, we directly examined how peptide/MHC ligands expressed on thymic epithelial cells trigger the positive selection of immature thymocytes. We demonstrate that abundant self-peptides, purified from the H-2D(b) molecules of thymic epithelial cells, are specifically recognized during the positive selection of CD8+ T cells, implying that positive selection generates a repertoire of T cells that is weakly self-reactive. We also found that this recognition is somewhat cross-reactive, thereby providing an explanation for how the specific recognition of a limited repertoire of thymic self-peptides can select a diverse repertoire of T cells.
authors.affiliation: Gwen Knapp Center for Lupus and Immunology Research, Department of Pathology, University of Chicago, Illinois 60637, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Hu
authors.forename: C R
authors.initials: CR
authors.lastname: Bazemore Walker
authors.forename: C
authors.initials: C
authors.lastname: Girao
authors.forename: J T
authors.initials: JT
authors.lastname: Opferman
authors.forename: J
authors.initials: J
authors.lastname: Sun
authors.forename: J
authors.initials: J
authors.lastname: Shabanowitz
authors.forename: D F
authors.initials: DF
authors.lastname: Hunt
authors.forename: P G
authors.initials: PG
authors.lastname: Ashton-Rickardt
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology* / Q000302:isolation & purification; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D004848:Epithelium / Q000276:immunology; D005260:Female; D005333:Fetus; D008213:Lymphocyte Activation; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000276:immunology* / Q000302:isolation & purification; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
chemical_list: D001324:Autoantigens; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta