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.