Class I MHC-peptide interactions: structural requirements and functional implications.
In this chapter, we have defined the structural motifs that dictate the capacity of peptides to bind to five different HLA-A alleles that represent some of the most common alleles found in different ethnic populations. In general, these peptide motifs were very specific for the individual HLA-A alleles, with the exception of HLA-A degree 0301 and HLA-A degree 1101, for which the motifs were very similar. When these motifs were tested against an unbiased and complete set of nonamer peptides derived from human papillomavirus E6 and E7 proteins, it was found that the vast majority of high and intermediate binding peptides contained the appropriate motif. Furthermore, using the dominant anchor residues, together with the amino acid positions that interact with secondary anchor residues, it was possible to predict high and intermediate binders. Finally, the finding that there is a direct correlation between binding affinity for MHC and immunogenicity suggests a practical application of being able to predict those peptides that have a high affinity binding for a particular MHC allele--that is, in the design of peptide based vaccines for prophylactic or therapeutic use.
Grey
H M
HM
Cytel, San Diego, California 92121, USA.
Ruppert
J
J
Vitiello
A
A
Sidney
J
J
Kast
W M
WM
Kubo
R T
RT
Sette
A
A
D000483:Alleles; D000595:Amino Acid Sequence; D000939:Epitopes / Q000276:immunology; D005006:Ethnicity / Q000235:genetics; D005805:Genes, MHC Class I / Q000276:immunology*; D015234:HLA-A Antigens / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000939:Epitopes; D015234:HLA-A Antigens; D010455:Peptides; D011948:Receptors, Antigen, T-Cell