Designing and maintaining the mature TCR repertoire: the continuum of self-peptide:self-MHC complex recognition.
Peripheral T cell maintenance requires a survival signal delivered upon T cell receptor (TCR)-major histocompatibility complex (MHC) molecule interaction. Since self-peptides play a critical role in the intrathymic positive selection of the mature TCR repertoire, we hypothesized an equally important role in T cell persistence. We used mice with a normal expression of MHC class II molecules but a restricted self-peptide complexity (H-2M alpha-/-) to show that an MHC class II-restricted T cell specificity that displays a deficient positive selection in the H-2M alpha-/- thymus shows an impaired persistence after adoptive transfer in H-2M alpha-/- recipients. Finally, a wild-type CD4+ TCR repertoire is incompletely maintained in H-2M alpha-/- recipients. These observations suggest that, similar to intrathymic positive selection, the maintenance of the mature TCR repertoire relies on the recognition of self-peptide:self-MHC complexes.
Viret
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C
Section of Immunobiology, Yale University School of Medicine and Howard Hughes Medical Institute, New Haven, Connecticut 06520-8011, USA.
Wong
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FS
Janeway
C A
CA
D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D002455:Cell Division / Q000528:radiation effects; D004347:Drug Interactions; D000939:Epitopes; D005260:Female; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000502:physiology*; D013934:Thymectomy
D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell