013 Uncovering antigen triggers in genetically predisposed psoriasis patients

Psoriasis (PsO) is a T cell-mediated autoimmune disease without cure. The major risk-associated PsO susceptibility gene encodes for the human leukocyte antigen C*06:02 (HLA-Cw6). Half of patients carry this allele encoding HLA-I molecule which presents short peptides (together known as immunopeptidome) to CD8 cells, thereby initiating immune responses. It unclear presented by HLA-Cw6 are prevalent trigger PsO. We generated immunopeptidomics data from skin-derived HLA-Cw6+ cell lines (>24,000 peptides) and newly HLA-Cw6Tg mouse model in conjunction with imiquimod-induced (>4,000 thus identifying set high relevance finding universal molecular triggers Strikingly, 58% characteristic 9-mer exclusive skin, were either identical or very similar (1 amino acid change) that we detected melanocyte/keratinocytes. To interrogate – interactions, performed single receptor sequencing clonal analysis skin cells lesional biopsies HLA-Cw6+/HLA-Cw6- patients. currently screening these receptors against our candidate establish dominant peptide broadly recognized autoreactive cells. conclude applying discovery new preclinical HLA-Cw6Tgmouse valid means study PsO-relevant immunopeptidome. Defining HLA-Cw6-restricted epitopes PsO, will facilitate therapeutic approaches develop tolerisation strategies potential achieve long-lasting remission.