Specificity and flexibility in thymic selection.
During positive selection, developing thymocytes are rescued from programmed cell death by T-cell receptor (TCR)-mediated recognition of major histocompatibility complex (MHC) molecules. MHC-bound peptides contribute to this process. Recently we identified individual MHC-binding peptides which can induce positive selection of a single TCR. Here we examine peptide fine specificity in positive selection. These data suggest that a direct TCR-peptide interaction occurs during this event, and strengthens the correlation between selecting peptides and TCR antagonists. Certain positively selecting peptides are weakly antigenic. We demonstrate that thymocytes 'educated' on such a peptide are specifically non-responsive to it and have decreased CD8 expression levels. Similar reduction of CD8 expression on mature T cells converts a TCR agonist into a TCR antagonist. These data indicate that thymocytes may maintain self-tolerance towards a positively selecting ligand by regulating co-receptor expression.
Jameson
S C
SC
Howard Hughes Medical Institute, Department of Immunology, University of Washington, Seattle 98195.
Hogquist
K A
KA
Bevan
M J
MJ
D000595:Amino Acid Sequence; D000818:Animals; D016827:CD8 Antigens / Q000096:biosynthesis; D002454:Cell Differentiation / Q000502:physiology; D002999:Clone Cells; D007108:Immune Tolerance; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009924:Organ Culture Techniques; D010047:Ovalbumin / Q000737:chemistry / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology*
D016827:CD8 Antigens; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin