title: Non-self-discrimination as a driving concept in the identification of an immunodominant HMW-MAA epitopic peptide sequence by autoantibodies from melanoma cancer patients.
abstract: We analyzed the sera of patients with melanoma to define the human humoral autoantibody profile towards HMW-MAA. Computational proteome scanning using the non-self-discrimination principle as a guide led to the individuation of the low-similarity HMW-MAA781-789RATVWMLRL peptide fragment as an immunodominant B-cell epitope. Linear B-cell determinant individuation was experimentally validated by dot blot immunoassay and NMR spectroscopy analysis. Regulation of physiologic self-reactivity by the non-self-discrimination principle is discussed.
authors.affiliation: Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dummer
authors.forename: Abraham
authors.initials: A
authors.lastname: Mittelman
authors.forename: Francesco P
authors.initials: FP
authors.lastname: Fanizzi
authors.forename: Guglielmo
authors.initials: G
authors.lastname: Lucchese
authors.forename: Jörg
authors.initials: J
authors.lastname: Willers
authors.forename: Darja
authors.initials: D
authors.lastname: Kanduc
mesh_terms: D000951:Antigens, Neoplasm / Q000737:chemistry* / Q000276:immunology*; D001323:Autoantibodies / Q000032:analysis*; D019295:Computational Biology; D000939:Epitopes; D006801:Humans; D007118:Immunoassay; D009682:Magnetic Resonance Spectroscopy; D008545:Melanoma / Q000276:immunology*; D020543:Proteome; D020539:Sequence Analysis, Protein; D012878:Skin Neoplasms / Q000276:immunology*; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000951:Antigens, Neoplasm; D001323:Autoantibodies; D000939:Epitopes; D020543:Proteome; D000099216:Chondroitin Sulfate Proteoglycan 4