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

McHugh, K; Rysnik, O; Kollnberger, S; Shaw, J; Utriainen, L; Al-Mossawi, H; Payeli, S; Marroquin, O; Milling, S; Renner, C; Bowness, P

Journal article

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

Abstract:: OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Publication status:: Published

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APA Style

McHugh, K., Rysnik, O., Kollnberger, S., Shaw, J., Utriainen, L., Al-Mossawi, H., Payeli, S., Marroquin, O., Milling, S., Renner, C., & Bowness, P. (2014). Expression of aberrant HLA-B27 molecules is dependent on B27 dosage and peptide supply. Annals of the Rheumatic Diseases, 73(4), 763–770.

MLA Style

McHugh, K., et al. “Expression of Aberrant HLA-B27 Molecules Is Dependent on B27 Dosage and Peptide Supply.” Annals of the Rheumatic Diseases, vol. 73, no. 4, 2014, pp. 763–70.

Chicago Style

McHugh, K, O Rysnik, S Kollnberger, J Shaw, L Utriainen, H Al-Mossawi, S Payeli, et al. 2014. “Expression of Aberrant HLA-B27 Molecules Is Dependent on B27 Dosage and Peptide Supply.” Annals of the Rheumatic Diseases 73 (4): 763–70.
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