Non-self-discrimination as a driving concept in the identification of an immunodominant HMW-MAA epitopic peptide sequence by autoantibodies from melanoma cancer patients.
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.
Dummer
Reinhard
R
Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
Mittelman
Abraham
A
Fanizzi
Francesco P
FP
Lucchese
Guglielmo
G
Willers
Jörg
J
Kanduc
Darja
D
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
D000951:Antigens, Neoplasm; D001323:Autoantibodies; D000939:Epitopes; D020543:Proteome; D000099216:Chondroitin Sulfate Proteoglycan 4