SPONDYLOARTHROPATHIES: Edited by Joerg ErmannMHC class I associations beyond HLA-B27: the peptide binding hypothesis of psoriatic arthritis and its implications for disease pathogenesisWinchester, Roberta; FitzGerald, OliverbAuthor Information aColumbia University, College of Physicians and Surgeons, New York City, NY, USA bUniversity College, Dublin, Ireland Correspondence to Robert Winchester, Columbia University Medical Center, 720 West 168th Street, New York City, NY 10032, NY. Tel: +1 212 305 6327; e-mail: firstname.lastname@example.org Current Opinion in Rheumatology: July 2020 - Volume 32 - Issue 4 - p 330-336 doi: 10.1097/BOR.0000000000000720 Buy Metrics Abstract Purpose of review To provide an overview of the heterogeneous human leucocyte antigen (HLA) associations of psoriatic arthritis, their relationship to particular clinical features of the disease, and how a hypothesis of binding specific peptides could provide a unifying basis for this heterogeneity. Recent findings There have been substantive advances in understanding the role of HLA molecules in binding self-peptides that select our repertoire of T cells, the specific peptide-binding properties of these HLA allotypes, and their crystallographic structure. These advances provide a means to envision the significance of the heterogeneous psoriatic arthritis HLA associations. The clinical relevance of these allotypes if heightened by emerging knowledge of their relationship to particular clinical features of the disease that serve as subphenotypes. Summary We propose a peptide binding hypothesis of psoriatic arthritis based on a shared pattern of negative charge in the ‘B’ pocket of the HLA-B and HLA-C molecules encoded by the susceptibility allotypes. This hypothesis suggests that peptides characterized by the presence of arginine at position 2 or 3 are bound to the susceptibility allotypes and drive the T-cell clones selected on them to attack molecules containing these peptides located in sites of psoriatic arthritis inflammation. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.