Requirement for diverse, low-abundance peptides in positive selection of Tcells

Whether a single major histocompatibility complex (MHC)-bound peptide can d rive the positive selection of large numbers of T cells has been-a controve rsial. issue. A diverse population of self peptides was shown to be essenti al for the in vivo development of CD4 T cells. Mice in which all but 5 perc ent of MHC class II molecules were bound by a single peptide had wild-type numbers of CD4 T cells. However, when the diversity within this 5 percent w as lost, CD4 T cell development was impaired. Blocking the major peptide-MH C complex in thymus organ culture had no effect on T cell development; indi cating that positive selection occurred on the diverse peptides present at low levels, This requirement for peptide diversity indicates that the inter action between self peptides and T cell receptors during positive selection is highly specific.