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 cell s 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 invari ant chain (li) (A(b)li(-)) and their transgenic variant (A(b)A(b)Epli(-)) t hat co-expresses Ab molecules covalently bound with a single peptide Ep(52- 68), In these latter mice, close to 50% of all Ab molecules are occupied by Ep(52-68) peptide. Although the A(b)Ep complex was abundantly expressed in the thymus under conditions excluding negative selection on bone marrow-de rived cells, no striking quantitative difference between repertoires of Ton expressed on CD4(+) T cells in Abli(-) and AbAbEpli(-) mice was noticed. O ur results are consistent with the view that diverse, low-abundance self-pe ptides play an important role in thymic positive selection and do not suppo rt the notion that dominant, high-abundance peptides may be critical for sh aping the TCR repertoire.