Specificity of peptide binding by the HLA-A2.1 molecule.
The HLA-A2 molecule contains a putative peptide binding site that is bounded by two alpha-helices and a beta-pleated sheet floor. Previous studies have demonstrated that the influenza virus matrix peptide M1 55-73 can sensitize target cells for lysis by HLA-A2.1-restricted virus-immune CTL and can induce CTL that can lyse virus-infected target cells. To assess the specificity of peptide binding by the HLA-A2.1 molecule, we examined the ability of seven variant M1 peptides to be recognized by a panel of M1 55-73 peptide-specific HLA-A2.1-restricted CTL lines. The results demonstrate that five out of the seven variant M1 55-73 peptides could be recognized by A2.1-restricted M1 55-73 peptide-specific CTL lines. The two variant peptides that were not recognized by any CTL could bind to HLA-A2.1 as indicated by their ability to compete for presentation of the M1 55-73 peptide. In addition, 5 of a panel of 24 unrelated peptides tested could also compete for M1 55-73 presentation by HLA-A2.1. One peptide derived from the sequence of a rotavirus protein could sensitize HLA-A2.1+ targets for lysis by M1 55-73 peptide-specific CTL. We conclude from these studies that: 1) the HLA-A2.1 molecule can bind a broad spectrum of peptides; 2) T cells selected for the ability to recognize one peptide plus a class I molecule can actually recognize an unrelated peptide presented by that same class I molecule; and 3) a stretch of three adjacent hydrophobic amino acids may be an important common feature of peptides that can bind to HLA-A2.1.
Shimojo
N
N
Molecular Immunology Section, National Institute of Neurological Disorders and Bethesda, MD 20892.
Maloy
W L
WL
Anderson
R W
RW
Biddison
W E
WE
Coligan
J E
JE
D000595:Amino Acid Sequence; D000938:Antigen-Presenting Cells / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology*; D001665:Binding Sites; D001667:Binding, Competitive; D015234:HLA-A Antigens / Q000378:metabolism*; D006801:Humans; D009980:Influenza A virus / Q000276:immunology; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism; D012401:Rotavirus / Q000276:immunology; D013329:Structure-Activity Relationship; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism*; D014763:Viral Matrix Proteins / Q000276:immunology* / Q000378:metabolism
D000956:Antigens, Viral; D015234:HLA-A Antigens; D009842:Oligopeptides; D014763:Viral Matrix Proteins