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Prinz, Jörg Christoph (2017): Melanocytes: Target Cells of an HLA-C*06:02-Restricted Autoimmune Response in Psoriasis. In: Journal of investigative Dermatology, Vol. 137, No. 10: pp. 2053-2058

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Abstract

HLA-C*06:02 is the main psoriasis risk allele. By the unbiased analysis of a V alpha 3S1/V beta 13S1T-cell receptor from pathogenic psoriatic CD8(+)T cells, we had recently proven that HLA-C*06:02 directs an autoimmune response against melanocytes through autoantigen presentation in psoriasis and identified ADAMTSL5 as a melanocyte autoantigen. We concluded that psoriasis is based on a melanocyte-specific immune response and that HLA-C*06:02 may predispose to psoriasis via this newly identified autoimmune pathway. Understanding this pathway, however, requires more detailed explanation. It is based on the fact that an HLA class I-restricted autoreactive CD8(+)T-cell response must be directed against a particular target cell type, because HLA class I molecules present peptide antigens generated from cytoplasmic (i.e., intracellular) proteins. This review summarizes the findings on the melanocyte-specific autoimmune response in the context of the immune mechanisms related to HLA function and T-cell receptor-antigen recognition. Identifying melanocytes as target cells of the psoriatic immune response now explains psoriasis as a primary autoimmune skin disease.

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