title: Computational peptide dissection of Melan-a/MART-1 oncoprotein antigenicity.
abstract: We have mapped the linear antigenic determinant of a commercial MAb raised in the mouse against the melanoma-associated-antigen Melan-A/MART-1. The B cell epitope on the Melan-A/MART-1 oncoprotein is located in the 15-mer amino acid sequence 101-115 PPAYEKLSAEQSPPP, within residues 102-106. The definition of the antigenic sequence on Melan-A/MART-1 oncoprotein was reached following analyses of MHC II binding potential and similarity level to the mouse proteome, that put into evidence the 15-mer amino acid sequence 101-115 PPAYEKLSAEQSPPP as the top scoring peptide in binding H2-A(d) molecules and the epitopic sequence residues 102-106 (i.e., the peptide sequence PAYEK) as having low-similarity level to the mouse proteome. Dot-blot epitope mapping immunoassay identified proline residue 102 as critical, based on its effect on antibody recognition. The present study adds to previous companion reports in validating the hypothesis that low-similarity to the host's proteome and binding potential to MHC II molecules are essential concurring factors in the modulation of the pool of epitopic sequences.
authors.affiliation: Department of Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA.
authors.forename: Raj
authors.initials: R
authors.lastname: Tiwari
authors.forename: Jan
authors.initials: J
authors.lastname: Geliebter
authors.forename: Alberta
authors.initials: A
authors.lastname: Lucchese
authors.forename: Abraham
authors.initials: A
authors.lastname: Mittelman
authors.forename: Darja
authors.initials: D
authors.lastname: Kanduc
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D019295:Computational Biology; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007118:Immunoassay; D015151:Immunoblotting; D058965:MART-1 Antigen; D008285:Major Histocompatibility Complex / Q000276:immunology; D008545:Melanoma / Q000276:immunology; D058950:Melanoma-Specific Antigens; D051379:Mice; D008958:Models, Molecular; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000737:chemistry / Q000276:immunology*; D015513:Oncogene Proteins / Q000737:chemistry / Q000276:immunology*; D010455:Peptides; D011392:Proline / Q000737:chemistry; D011485:Protein Binding / Q000276:immunology; D020543:Proteome
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000939:Epitopes; D058965:MART-1 Antigen; C548667:MLANA protein, human; D058950:Melanoma-Specific Antigens; C548668:Mlana protein, mouse; D009363:Neoplasm Proteins; D015513:Oncogene Proteins; D010455:Peptides; D020543:Proteome; D011392:Proline