On the role of high- and low-abundance class II MHC-peptide complexes in the thymic positive selection of CD4⁺ T cells

The role of self-peptides bound to MHC molecules in the selection of T cells in the thymus remains controversial. Here, we have tested whether a high-abundance single class II MHC-peptide complex has a dominant effect on the repertoire of CD4⁺ T cells selected by low-abundance class II MHC-peptide complexes. For these studies, we have used H-2^b mice that lack an invariant chain (li) (A^bli^-) and their transgenic variant (A^bA^bEpli^-) that co-expresses A^b molecules covalently bound with a single peptide Ep(52-68). In these latter mice, close to 50% of all A^b molecules are occupied by Ep(52-68) peptide. Although the A^bEp complex was abundantly expressed in the thymus under conditions excluding negative selection on bone marrow-derived cells, no striking quantitative difference between repertoires of TCR expressed on CD4⁺ T cells in A^bli^- and A^bA^bEpli^- mice was noticed. Our results are consistent with the view that diverse, low-abundance self-peptides play an important role in thymic positive selection and do not support the notion that dominant, high-abundance peptides may be critical for shaping the TCR repertoire.