ALANINE SCANNING MUTAGENESIS OF AN ALPHA-BETA-T-CELL RECEPTOR - MAPPING THE ENERGY OF ANTIGEN RECOGNITION

The T cell receptor (TCR) from the alloreactive T lymphocyte 2C recogn izes a nonamer peptide QL9 complexed with the MHC class I molecule H2- L-d. Forty-two single-site alanine substitutions of the 2C TCR were an alyzed for binding to QL9/L-d and anti-TCR antibodies. The results pro vided a detailed energy map of T cell antigen recognition and indicate d that the pMHC and clonotypic antibody epitopes on the TCR were simil ar. Although residues in each V alpha and V beta CDR are important in binding pMHC, the most significant energy for the TCR/QL9/L-d interact ion was contributed by CDRs 1 and 2 of both alpha and beta chains. The extent to which the individual energy contributions are directed at c lass I helices or peptide was also assessed.