Definition of anti-tyrosinase MAb T311 linear determinant by proteome-based similarity analysis.
Using non-self discrimination as a driving force in generating peptide immunogenicity, we have developed a computer-assisted proteomic analysis in order to identify the protein antigenic regions that have evoked humoral response. The purpose of this study was to further validate the computational analysis for melanoma-associated antigens and, at the same time, to assess the efficacy of the methodology in defining antigenic regions of autoantigens associated to autoimmune diseases. To achieve this two-fold objective, we have examined the enzyme tyrosinase, a protein that represents an important autoantigen in patients with vitiligo or melanoma. Here, we report that the antigenic linear determinant of the monoclonal antibody (Mab) T311 raised against the melanoma/vitiligo tyrosinase autoantigen is located in the low similarity 15-mer amino acid sequence tyrosinase 233-247 IPYWDWRDAEKCDIC, within the fragment 237-247. These data confirm non-similarity to the host proteome as a factor that participates in shaping peptide immune reactivity and may be a first step towards designing tyrosinase antigenic peptides to be used for (i) direct neutralization of harmful melanocytes-attacking autoantibodies in vitiligo, or (ii) production of antibodies against tyrosinase-positive melanomas. Moreover tyrosinase peptide antigens might be used as key tools in studying the boundaries between self-tolerance and autoimmunity phenomena.
Willers
Jörg
J
Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
Lucchese
Alberta
A
Mittelman
Abraham
A
Dummer
Reinhard
R
Kanduc
Darja
D
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000235:genetics; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry / Q000235:genetics; D006183:H-2 Antigens / Q000378:metabolism; D006801:Humans; D008545:Melanoma / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D014442:Monophenol Monooxygenase / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D040901:Proteomics
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000939:Epitopes; D006183:H-2 Antigens; D010446:Peptide Fragments; D014442:Monophenol Monooxygenase