Identification of the nonamer peptide from influenza A matrix protein and the role of pockets of HLA-A2 in its recognition by cytotoxic T lymphocytes.
Influenza matrix peptide 58-66 is shown to be the optimal nonamer for binding to HLA-A2 and presentation to cytotoxic T lymphocytes (CTL). If titered out to 2 x 10(-10) - 4 x 10(-10) M in CTL-mediated lysis assays and to 3 x 10(-9) M in an HLA-A2 assembly-stabilization assay in cell lysates. The peptide was shown to make probable contacts with its carboxy terminus close to residue 116 in the floor of the cleft of HLA-A2, close to the F pocket. The side chain of the amino-terminal amino acid was unimportant, but its free amino and carbonyl groups in the A pocket appeared important in optimizing peptide presentation. The B pocket probably accommodates the side chain of residue 2 (isoleucine) and was shown to be critical in peptide presentation.
Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, GB.
J
J
Morrison
J
J
Elvin
F
F
Latron
F
F
Gotch
R
R
Moots
J L
JL
Strominger
A
A
McMichael
D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000737:chemistry / Q000276:immunology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D000939:Epitopes; D015789:HLA-A2 Antigen / Q000737:chemistry / Q000276:immunology*; D066298:In Vitro Techniques; D009980:Influenza A virus / Q000276:immunology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D013329:Structure-Activity Relationship; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000276:immunology*
D000956:Antigens, Viral; D000939:Epitopes; D015789:HLA-A2 Antigen; C031540:M-protein, influenza virus; D010455:Peptides; D014763:Viral Matrix Proteins