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 pep tide, CLIP, derived from the class II-associated invariant chain. Previous studies showed that H2-DM- cells are defective in presenting synthetic pept ides to class II-restricted T cells, In sharp contrast, however, the same p eptides elicited strong CD4(+) T cell responses in H2-DM- animals. We now p rovide an explanation for this apparent discrepancy. Peptide-specific CD4() T cells from wild-type mice were efficiently stimulated by H2-DM+, but no t 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 additio n, unlike Ag-specific T cells from wild-type animals, the reactivities of p eptide-specific T cells from mutant animals could not be efficiently blocke d by Abs specific for the cognate MHC class II-peptide combination. We furt her demonstrated that the distinct reactivities of CD4(+) T cells from H2-D M+ 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.