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Antigen Processing, Presentation, and Tolerance: Role in Autoimmune Skin Diseases

  • Jörg Christoph Prinz
    Correspondence
    Correspondence: Jörg Christoph Prinz, Department of Dermatology and Allergy, University Hospital, Ludwig-Maximilian-University of Munich, Frauenlobstrasse 9-11, Munich D-80337, Germany.
    Affiliations
    Department of Dermatology and Allergy, University Hospital, Ludwig-Maximilian-University of Munich, Munich, Germany
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      Autoreactive T cells pose a constant risk for the emergence of autoimmune skin diseases in genetically predisposed individuals carrying certain HLA risk alleles. Immune tolerance mechanisms are opposed by broad HLA-presented self-immunopeptidomes, a predefined repertoire of polyspecific TCRs, the continuous generation of new antibody specificities by somatic recombination of Ig genes in B cells, and heightened proinflammatory reactivity. Increased autoantigen presentation by HLA molecules, cross-activation of pathogen-induced T cells against autologous structures, altered metabolism of self-proteins, and excessive production of proinflammatory signals may all contribute to the breakdown of immune tolerance and the development of autoimmune skin diseases.

      Abbreviations:

      BCR (B-cell receptor), BP (bullous pemphigoid), DC (dendritic cell), DPP4 (dipeptidyl peptidase IV), DSG (desmoglein), ER (endoplasmic reticulum), GPP (generalized pustular psoriasis), KC (keratinocyte), MHC (major histocompatibility complex), Th (T helper), Treg (regulatory T cell)
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