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In the Normal Repertoire of CD4⁺ T Cells, a Single Class II MHC/Peptide Complex Positively Selects TCRs with Various Antigen Specificities¹

Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912

In the thymus, immature T cells are positively and negatively selected by multiple interactions between their Ag receptors (TCRs) and self MHC/peptide complexes expressed on thymic stromal cells. Here we show that in the milieu of negative selection on physiological self class II MHC/peptide complexes (A^bwt), a single class II/peptide complex A^bEp_52–68 positively selects a number of TCRs with various Ag specificities. This TCR repertoire is semidiverse and not biased toward Ep-like Ags. Our finding implies that the degeneracy of positive selection for peptide ligands exceeds peptide-specific negative selection and is essential to increase the efficiency and diversity of the repertoire so that T cells with the same Ag specificity can be selected by different self MHC/peptide complexes.

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