THE IDENTIFICATION OF TYROSINE AS A COMMON KEY RESIDUE IN UNRELATED H-2KD RESTRICTED ANTIGENIC PEPTIDES

We have compared the activity of several K(d)- or L(d)-restricted antigenic peptides as competitors in a functional competition assay using cytolytic T lymphocyte (CTL) clones. All of four unrelated K(d)-restricted peptides tested could compete with each other but not with the L(d)-restricted peptide P91A-.12-24 (P91A). Moreover, the P91A peptide failed to compete with the four K(d)-restricted peptides. In contrast, another L(d)-restricted peptide [mouse cytomegalovirus (MCMV) pp89 167-176] could clearly compete with both K(d)- and L(d)-restricted peptides. The comparison of a series of modified MCMV pp89 peptides suggested that distinct structural features allow the interaction of the peptide with the two different MHC class I molecules. We showed previously that the competitor activity of two different K(d)-restricted antigenic peptides was reduced substantially upon Ala substitution of the single Tyr residues present in these peptides. We now show a similar effect for two additional K(d)-restricted peptides. Our results thus suggest that Tyr may function as an 'anchor' residue for many antigenic peptides that bind to the K(d) molecule. Molecular modeling of the presumed antigen-binding site of the K(d) molecule revealed the presence of two deep cavities that may be involved in binding peptide amino acid side chains. A model illustrating one possible interaction of a Tyr-containing peptide with the K(d) molecule is presented.