PMID- 23625978 OWN - NLM STAT- MEDLINE DCOM- 20140429 LR - 20220129 IS - 1468-2060 (Electronic) IS - 0003-4967 (Linking) VI - 73 IP - 4 DP - 2014 Apr TI - Expression of aberrant HLA-B27 molecules is dependent on B27 dosage and peptide supply. PG - 763-70 LID - 10.1136/annrheumdis-2012-203080 [doi] AB - 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-CD3epsilon-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-CD3epsilon-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. FAU - McHugh, Kirsty AU - McHugh K AD - Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Science, University of Oxford, , Oxford, UK. FAU - Rysnik, Oliwia AU - Rysnik O FAU - Kollnberger, Simon AU - Kollnberger S FAU - Shaw, Jacqueline AU - Shaw J FAU - Utriainen, Lotta AU - Utriainen L FAU - Al-Mossawi, Mohammad Hussein AU - Al-Mossawi MH FAU - Payeli, Sravan AU - Payeli S FAU - Belaunzaran, Osiris Marroquin AU - Belaunzaran OM FAU - Milling, Simon AU - Milling S FAU - Renner, Christoph AU - Renner C FAU - Bowness, Paul AU - Bowness P LA - eng GR - 19380/VAC_/Versus Arthritis/United Kingdom GR - 18599/ARC_/Arthritis Research UK/United Kingdom GR - 19611/VAC_/Versus Arthritis/United Kingdom GR - 19807/VAC_/Versus Arthritis/United Kingdom GR - 19611/ARC_/Arthritis Research UK/United Kingdom GR - 19807/ARC_/Arthritis Research UK/United Kingdom GR - 19853/ARC_/Arthritis Research UK/United Kingdom GR - 19853/VAC_/Versus Arthritis/United Kingdom GR - 18599/VAC_/Versus Arthritis/United Kingdom GR - 19380/ARC_/Arthritis Research UK/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130426 PL - England TA - Ann Rheum Dis JT - Annals of the rheumatic diseases JID - 0372355 RN - 0 (Antibodies, Monoclonal) RN - 0 (HLA-B27 Antigen) RN - 0 (KIR3DL2 protein, human) RN - 0 (Peptides) RN - 0 (Receptors, KIR3DL2) SB - IM EIN - Ann Rheum Dis. 2016 Jun;75(6):1254. PMID: 27166138 MH - Aging/immunology MH - Animals MH - Antibodies, Monoclonal/immunology MH - Antigen-Presenting Cells/immunology MH - Cell Line MH - Coculture Techniques MH - *Gene Dosage MH - HLA-B27 Antigen/genetics/*metabolism MH - Humans MH - Hydrogen-Ion Concentration MH - Jurkat Cells MH - Peptides/*metabolism MH - Rats MH - Rats, Transgenic MH - Receptors, KIR3DL2/metabolism MH - Spleen/cytology/*immunology MH - Spondylarthritis/immunology EDAT- 2013/04/30 06:00 MHDA- 2014/04/30 06:00 CRDT- 2013/04/30 06:00 PHST- 2013/04/30 06:00 [entrez] PHST- 2013/04/30 06:00 [pubmed] PHST- 2014/04/30 06:00 [medline] AID - annrheumdis-2012-203080 [pii] AID - 10.1136/annrheumdis-2012-203080 [doi] PST - ppublish SO - Ann Rheum Dis. 2014 Apr;73(4):763-70. doi: 10.1136/annrheumdis-2012-203080. Epub 2013 Apr 26.