To test models of T-cell recognition, mice transgenic for T-cell receptor α or β chain have been immunized with variant peptides that force changes in the resulting T-cell response. In particular, charge substitutions on the peptide often elicit reciprocal charges in the junctional (CDR3) sequences of T-cell receptor V_αor V_β chains, indicating direct T-cell receptor–peptide contact, and allowing derivation of a topology for the T-cell receptor–MHC interaction. At one position on the peptide, variants transformed a homogeneous V^β response into a very heterogeneous one.