In the normal repertoire of CD4(+) T cells, a single class II MHC/peptide complex positively selects TCRs with various antigen specificities

In the thymus, immature T cells are positively and negatively selected by m ultiple interactions between their Ag receptors (TCRs) and self MHC/peptide complexes expressed on thymic stromal cells. Here we show that in the mili eu of negative selection on physiological self class II MHC/peptide complex es (A(b)wt), a single class II/peptide complex A(b)Ep(52-68) positively sel ects a number of TCRs with various Ag specificities, This TCR repertoire is semidiverse and not biased toward Ep-like Ags, Our finding implies that th e degeneracy of positive selection for peptide ligands exceeds peptide-spec ific negative selection and is essential to increase the efficiency and div ersity of the repertoire so that T cells with the same Ag specificity can b e selected by different self MHC/peptide complexes.