Highly restricted T cell repertoire shaped by a single major histocompatibility complex-peptide ligand in the presence of a single rearranged T cell receptor beta chain.
The T cell repertoire is shaped by positive and negative selection of thymocytes through the interaction of alpha/beta-T cell receptors (TCR) with self-peptides bound to self-major histocompatibility complex (MHC) molecules. However, the involvement of specific TCR-peptide contacts in positive selection remains unclear. By fixing TCR-beta chains with a single rearranged TCR-beta irrelevant to the selecting ligand, we show here that T cells selected to mature on a single MHC-peptide complex express highly restricted TCR-alpha chains in terms of Valpha usage and amino acid residue of their CDR3 loops, whereas such restriction was not observed with those selected by the same MHC with diverse sets of self-peptides including this peptide. Thus, we visualized the TCR structure required to survive positive selection directed by this single ligand. Our findings provide definitive evidence that specific recognition of self-peptides by TCR could be involved in positive selection of thymocytes.
Fukui
Y
Y
Department of Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Hashimoto
O
O
Inayoshi
A
A
Gyotoku
T
T
Sano
T
T
Koga
T
T
Gushima
T
T
Sasazuki
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015704:CD4 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D016827:CD8 Antigens / Q000032:analysis; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor / Q000276:immunology; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000276:immunology*; D005805:Genes, MHC Class I / Q000276:immunology*; D005802:Genes, MHC Class II / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000235:genetics; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism*
D015704:CD4 Antigens; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D008024:Ligands; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta