Specific recognition of thymic self-peptides induces the positive selection of cytotoxic T lymphocytes.
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.
Hu
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Gwen Knapp Center for Lupus and Immunology Research, Department of Pathology, University of Chicago, Illinois 60637, USA.
Bazemore Walker
C R
CR
Girao
C
C
Opferman
J T
JT
Sun
J
J
Shabanowitz
J
J
Hunt
D F
DF
Ashton-Rickardt
P G
PG
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*
D001324:Autoantigens; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta