Influence of infection of cells with bacteria associated with reactive arthritis on the peptide repertoire presented by HLA-B27

Department of Medical Microbiology, *E.C. Slater Institute and Department of Biochemistry, Academic Medical Center, University of Amsterdam, Department of Transplantation Immunology, Central Laboratory of the Blood Transfusion Service, Amsterdam and Arthron, Amsterdam, The Netherlands Corresponding author: Dr J.H. Ringrose (e-mail: j.ringrose @amc.uva.nl). Received 27 April 2000; revised version received 6 Sept. 2000; accepted 29 Sept. 2000. Abstract Reactive arthritis (ReA) after infections with various gram-negative bacteria is strongly associated with the MHC class I molecule HLA-B27. It is supposed that the B27 molecule itself plays a role in the pathogenesis of ReA by presenting antigenic peptides to cytotoxic T lymphocytes. The peptide repertoires presented by Salmonella - , Shigella - and non-infected cells were compared to identify such peptides. From the peptides isolated from the B27 molecules of these cells, profiles were generated by reversed-phase chromatography and peaks present in the profiles from infected cells but not in profiles from non-infected cells were studied for their peptide compositions. Some sequences with identity to those in human histone H3, human ribosomal protein S17 and the heavy chain of HLA-B27 itself were detected only in profiles from infected cells. All peptides identified from infected cells contained the B*2705 peptide-binding motif. The data suggest that HLA-B27-positive cells infected with ReA-inducing bacteria show an increased presentation of certain self-peptides. There was no evidence for altered peptide-binding specificity of B27 after infection. However, the interpretations were hampered by the variation in peptide presentation between different experiments.