T cells can be activated by peptides that are unrelated in sequence to their selecting peptide.

We tested the ability of CD4+ T cells, selected in the thymus by reaction with class II protein bound to a single peptide, to react with the same class II protein bound to other peptides. The T cells reacted with all peptides tested, including one that was quite unlike the selecting peptide in T cell receptor binding residues. The receptors on class II/peptide-reactive T cells from class II/single peptide mice were similar but not identical to some of those from normal animals. Thus, class II bound to a single peptide selects a subset of T cells that is related to that selected by class II bound to many peptides.