MAPPING T-CELL RECEPTOR PEPTIDE CONTACTS BY VARIANT PEPTIDE IMMUNIZATION OF SINGLE-CHAIN TRANSGENICS

To test models of T-cell recognition, mice transgenic for T-cell receptor-alpha or beta-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(alpha) or V(beta) 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(beta) response into a very heterogeneous one.