Immune responses contribute to the pathogenesis of
vitiligo and target
melanoma sometimes associated with
vitiligo-like depigmentation in some
melanoma patients. We analyzed the sera from patients with
vitiligo and cutaneous
melanoma for reactivity toward
tyrosinase peptide sequences 1) endowed with low level of similarity to human
proteome, and 2) potentially able to bind HLA-DR1 Ags. We report that the
tyrosinase autoantigen was immunorecognized with the same molecular pattern by sera from
vitiligo and
melanoma patients. Five
autoantigen peptides composed the immunodominant anti-
tyrosinase response: aa95-104FMGFNCGNCK; aa175-182 LFVWMHYY; aa176-190FVWMHYYVSMDALLG; aa222-236IQKLTGDENFTIPYW, and aa233-247 IPYWDWRDAEKCDIC. All of the five antigenic
peptides were characterized by being (or containing) a sequence with low similarity level to the self
proteome. Sera from healthy subjects were responsive to aa95-104FMGFNCGNCK, aa222-236IQKLTGDENFTIPYW, and aa233-247 IPYWDWRDAEKCDIC, but did not react with the aa175-182LFVWMHYY and aa176-190FVWMHYYVSMDALLG
peptide sequences containing the
copper-binding His180 and the
oculocutaneous albinism I-A variant position F176. Our results indicate a clear-cut link between
peptide immunogenicity and low similarity level of the corresponding amino acid sequence, and are an example of a comparative analysis that might allow to comprehensively distinguish the
epitopic peptide sequences within a disease from those associated to natural
autoantibodies. In particular, these data, for the first time, delineate the linear B
epitope pattern on
tyrosinase autoantigen and provide definitive evidence of humoral immune responses against
tyrosinase.