The peptide binding specificity of HLA class I molecules is largely allele-specific and non-overlapping.
To understand better the specificity of peptide binding by MHC class I molecules, we have evaluated the capacity of a panel of unrelated peptides to compete for the presentation of viral peptides presented by HLA-A3 and HLA-B27. The HIV-Nef7F peptide (74-82) was presented by HLA-A3 to Nef-specific HLA-A3-restricted CTL lines, and the influenza nucleoprotein peptide NP(380-393) was presented by HLA-B27 to NP(380-393)-specific HLA-B27-restricted CTL lines. In addition, we have extended studies from our group that have evaluated the capacity of a similar panel of peptides to inhibit presentation of an influenza nucleoprotein peptide NP (335-349) by HLA-B37 and a matrix peptide, M1 (57-68), by HLA-A2 to the appropriate peptide-specific CTL lines. Out of 41 peptides tested, only five bound to more than one of the MHC molecules analyzed. Pairwise comparisons of the peptide binding specificities among these four different class I molecules revealed no common competitor peptides in four of the six possible comparisons. Thus, each class I molecule appears to have a functionally distinct peptide binding site, as reflected by the ability to bind largely non-overlapping sets of peptides.
Carreno
B M
BM
Molecular Immunology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
Koenig
S
S
Coligan
J E
JE
Biddison
W E
WE
D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D001667:Binding, Competitive; D000939:Epitopes / Q000235:genetics*; D015789:HLA-A2 Antigen / Q000378:metabolism; D015791:HLA-A3 Antigen / Q000378:metabolism; D015235:HLA-B Antigens / Q000378:metabolism; D015796:HLA-B27 Antigen / Q000378:metabolism; D059912:HLA-B37 Antigen; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009980:Influenza A virus / Q000276:immunology; D008969:Molecular Sequence Data; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D016601:RNA-Binding Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014758:Viral Core Proteins / Q000276:immunology / Q000378:metabolism
D000939:Epitopes; D015789:HLA-A2 Antigen; D015791:HLA-A3 Antigen; D015235:HLA-B Antigens; D015796:HLA-B27 Antigen; D059912:HLA-B37 Antigen; D015395:Histocompatibility Antigens Class I; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins