BINDING OF ALANINE-SUBSTITUTED PEPTIDES TO THE MHC CLASS-I PROTEIN, KD

Peptides eluted from the native MHC class I molecule, K(d) are generally nonamers that display a strong preference for Tyr in position 2. We investigated the molecular basis for this 'consensus motif' by synthesizing a virally derived peptide, NP 147-155, that is known to be presented by K(d) on living cells, and peptide variants of NP 147-155 in which the amino acids in the different positions were sequentially replaced by Ala. All of the peptides bound to purified K(d) molecules in vitro with high affinity, except for the peptide in which Tyr2 was replaced by Ala, for which the affinity for K(d) decreased at least 100-fold. These results confirm the interpretation of the in vivo studies; namely, that Tyr2 is a critical anchor residue for binding to K(d).