Unexpected reactivities of T cells selected by a single MHC-peptide ligand.
In H2-DM mutant mice, most MHC class II molecules are bound by a single peptide, CLIP, derived from the class II-associated invariant chain. Previous studies showed that H2-DM- cells are defective in presenting synthetic peptides to class II-restricted T cells. In sharp contrast, however, the same peptides elicited strong CD4+ T cell responses in H2-DM- animals. We now provide an explanation for this apparent discrepancy. Peptide-specific CD4+ T cells from wild-type mice were efficiently stimulated by H2-DM+, but not by H2-DM- cells pulsed with the cognate peptide. In sharp contrast, CD4+ T cells from mutant animals specific for the same MHC-peptide combination recognized peptide-pulsed H2-DM+ and H2-DM- cells equally well. In addition, unlike Ag-specific T cells from wild-type animals, the reactivities of peptide-specific T cells from mutant animals could not be efficiently blocked by Abs specific for the cognate MHC class II-peptide combination. We further demonstrated that the distinct reactivities of CD4+ T cells from H2-DM+ and H2-DM- mice are due to differences in thymic selection. Collectively, these findings indicate that the CD4+ T cell repertoires of H2-DM+ and H2-DM- mice are remarkably different.
Singh
N
N
Howard Hughes Medical Institute, Department of Microbiology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Van Kaer
L
L
D000595:Amino Acid Sequence; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017951:Antigen Presentation / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006681:HLA-D Antigens / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II; D006822:Hybrid Cells / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D018984:Epitopes, T-Lymphocyte; C416189:H2-M antigens; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D000949:Histocompatibility Antigens Class II; D008024:Ligands; D010455:Peptides