Dynamic tuning of T cell reactivity by self-peptide-major histocompatibility complex ligands.
Intrathymic self-peptide-major histocompatibility complex class II (MHC) molecules shape the T cell repertoire through positive and negative selection of immature CD4(+)CD8(+) thymocytes. By analyzing the development of MHC class II-restricted T cell receptor (TCR) transgenic T cells under conditions in which the endogenous peptide repertoire is altered, we show that self-peptide-MHC complexes are also involved in setting T cell activation thresholds. This occurs through changes in the expression level of molecules on thymocytes that influence the sensitivity of TCR signaling. Our results suggest that the endogenous peptide repertoire modulates T cell responsiveness in the thymus in order to enforce tolerance to self-antigens.
Wong
P
P
Department of Immunology and Howard Hughes Medical Institute, University of Washington School of Medicine, Seattle,Washington 98195, USA.
Barton
G M
GM
Forbush
K A
KA
Rudensky
A Y
AY
D000818:Animals; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D018956:CD5 Antigens; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology*; D037181:Lectins, C-Type; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D012641:Selection, Genetic; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D018956:CD5 Antigens; D000949:Histocompatibility Antigens Class II; D037181:Lectins, C-Type; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D000099192:CD69 Antigens