Positive selection of the T-cell repertoire is affected by mutations in the peptide-binding site of MHC class I molecules.
H-2Kb mutant molecules (H-2Kbm) and the H-2Kb-restricted response to OVA and VSV N peptides were used to investigate the influence of polymorphism of structurally defined regions of the MHC class I molecules on intrathymic positive selection of the T-cell repertoire. We show that the positive selection of the T-cell repertoire in the thymus requires the self-peptide to be present in the MHC antigen-binding site. A correlation between the ability of four MHC molecules to present antigenic peptide and to positively select T cells specific for it was noted. The self-peptides involved in positive selection may therefore mimic the foreign peptide during intrathymic selection. A structural correlate of this mimicry may be a similar or identical binding requirement for the antigen-binding pocket(s)/residues of the MHC peptide-binding site.
Laboratory of T Cell Development, Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
J
J
Nikolić-Zugić
R
R
Dyall
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001665:Binding Sites; D002213:Capsid / Q000276:immunology; D005805:Genes, MHC Class I; D006183:H-2 Antigens / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D017354:Point Mutation; D011828:Radiation Chimera; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology; D014758:Viral Core Proteins / Q000276:immunology
D006183:H-2 Antigens; D014758:Viral Core Proteins; D010047:Ovalbumin