Expression of aberrant HLA-B27 molecules is dependent on B27 dosage and peptide supply

McHugh, K. et al. (2014) Expression of aberrant HLA-B27 molecules is dependent on B27 dosage and peptide supply. Annals of the Rheumatic Diseases, 73(4), pp. 763-770. (doi: 10.1136/annrheumdis-2012-203080)

Abstract

<b>Objectives</b> Cellular expression of non-classical forms of human leukocyte antigen (HLA)-B27 (NC-B27) may be involved in spondyloarthritis (SpA) pathogenesis. We used a novel B27-specific monoclonal antibody, HD6, to ask if B27 transgenic (TG) rat splenocytes express these NC-B27 molecules. We also investigated whether B27-binding peptides could affect the expression and functional immune recognition of HD6-reactive B27 molecules.<p></p> <b>Methods</b> Splenocytes from B27-TG, B7-TG and non-transgenic rats, and HLA-B27+ cell lines were stained with monoclonal antibodies recognising classical (ME-1, HLA-ABC-m1) and non-classical (HD6, HC10) B27. Cells were further cultured in the presence of HLA-B27-binding peptides, or subjected to brief low pH treatment prior to mAb staining and/or immunoprecipitation or co-culture with KIR3DL2-CD3ε-expressing Jurkat reporter cells.<p></p> <b>Results</b> HD6-reactive molecules were detected in the majority of adult B27-TG rat splenocyte cell subsets, increasing with age and concomitant increased B27 expression. HD6 staining was inhibited by incubation with B27-binding peptides and induced by low pH treatment. HD6 staining correlated with KIR3DL2-CD3ε-expressing Jurkat reporter cell activity. Thus, IL-2 production was decreased when B27-expressing antigen-presenting cells were preincubated with B27-binding peptides, but increased following pretreatment with low pH buffer.<p></p> <b>Conclusions</b> Surface expression of HD6-reactive B27 molecules on B27-TG rat splenocytes is consistent with a pathogenic role for NC-B27 in SpA. Interaction of NC-B27 with innate immune receptors could be critical in SpA pathogenesis, and we show that this may be influenced by the availability and composition of the B27-binding peptide pool.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Milling, Professor Simon and Utriainen, Dr Lotta
• Authors: McHugh, K., Rysnik, O., Kollnberger, S., Shaw, J., Utriainen, L., Al-Mossawi, M. H., Payeli, S., Marroquin, O., Milling, S., Renner, C., and Bowness, P.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Annals of the Rheumatic Diseases
• Publisher: BMJ Group
• ISSN: 0003-4967
• ISSN (Online): 1468-2060