DEFICIENT POSITIVE SELECTION OF CD4 T-CELLS IN MICE DISPLAYING ALTERED REPERTOIRES OF MHC CLASS II-BOUND SELF-PEPTIDES

The role of self-peptides in positive selection of CD4(+) T cells has been controversial. We show that some self-peptides are presented by t he MHC class II molecule I-A(b) in mice lacking ii or H-2M but not in mice expressing a transgene-encoded peptide fused to I-A(b). In experi ments using specific antibodies to block selection, these low-abundanc e self-peptides were implicated in the positive selection of some CD4( +) T cells in H-2M(-/-) mice. However, all three mutant backgrounds fa iled to positively select two class II-restricted transgenic T cell re ceptors. Our findings suggest that minor components of the self-peptid e repertoire can contribute to positive selection of a significant num ber of CD4(+) T cells. In addition, the data suggest that T ce!ll rece ptor repertoires selected in wild-type mice and in mice displaying lim ited spectra of self-peptides are distinct.