The influence of individual peptides in thymic selection was examined in H2-M- mice, in which positive selection is directed to a single peptide, class II-associated invariant chain peptide (CLIP) bound to H2-Ab. Two sensitive in vivo approaches showed that 70%-80% of CD4+ T cells undergoing positive selection to CLIP+H2-Ab have self-reactivity to the various peptides expressed on wild-type H2-M+ antigen-presenting cells. When these self-reactive T cells were depleted, the residual CD4+ cells displayed a polyclonal repertoire in terms of alloreactivity, responses to foreign protein antigens, and Vβ usage. Nevertheless, studies with two T cell receptor transgenic lines suggested that the repertoire of CD4+ cells induced by CLIP was less diverse than the repertoire of CD4+ cells in normal mice. Generation of a fully diverse T cell repertoire thus requires positive selection against multiple peptides.
Surh, C. D., Lee, D. S., Fung-Leung, W. P., Karlsson, L., & Sprent, J. (1997). Thymic selection by a single MHC/peptide ligand produces a semidiverse repertoire of CD4+ T cells. Immunity, 7(2), 209–219. https://doi.org/10.1016/S1074-7613(00)80524-5