title: Positioning of a peptide in the cleft of HLA-A2 by complementing amino acid changes.
abstract: Several mutant HLA-A2 molecules have been constructed and expressed in the mutant human B-cell line C1R, which lacks HLA-A and HLA-B antigens, and examined for presentation of a previously defined peptide epitope derived from the influenza matrix protein to appropriate human cytotoxic T-lymphocyte lines. When leucine residue 66 in this matrix peptide containing residues 57-68 (matrix peptide 57-68) was replaced by arginine, the resulting matrix peptide 57-68 R66 was not presented to HLA-A2, but the mutation Y116D (tyrosine to aspartic acid at residue 116) in the floor of the peptide binding cleft near its right end dramatically restored peptide presentation. A similar result was obtained by substitution of ornithine for leucine at residue 66. These data provide strong support for a model in which the peptide is orientated with its amino terminus at the left end of the cleft of HLA-A2 and its carboxyl terminus at the right.
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
authors.forename: F
authors.initials: F
authors.lastname: Latron
authors.forename: R
authors.initials: R
authors.lastname: Moots
authors.forename: J B
authors.initials: JB
authors.lastname: Rothbard
authors.forename: T P
authors.initials: TP
authors.lastname: Garrett
authors.forename: J L
authors.initials: JL
authors.lastname: Strominger
authors.forename: A
authors.initials: A
authors.lastname: McMichael
mesh_terms: D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000276:immunology; D001665:Binding Sites; D002460:Cell Line; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000235:genetics; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology*; D006801:Humans; D009980:Influenza A virus / Q000276:immunology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000276:immunology; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic; D014162:Transfection; D014763:Viral Matrix Proteins / Q000276:immunology*
chemical_list: D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D011994:Recombinant Proteins; D014763:Viral Matrix Proteins