The arthritis-associated HLA-B*27:05 allele forms more cell surface B27 dimer and free heavy chain ligands for KIR3DL2 than HLA-B*27:09

Alberto Cauli, Jacqueline Shaw, Joanna Giles, Hiroko Hatano, Oliwia Rysnik, Sravan Payeli, Kirsty McHugh, Grazia Dessole, Giovanni Porru, Elisabetta Desogus, Sarah Fiedler, Soraya Hölper, Amanda Carette, Miguel Angel Blanco-Gelaz, Alessandra Vacca, Matteo Piga, Valentina Ibba, Pietro Garau, Giorgio La Nasa, Carlos López-LarreaAlessandro Mathieu, Christoph Renner, Paul Bowness, Simon Kollnberger

Research output: Contribution to journalArticlepeer-review

48 Citations (Scopus)

Abstract

Objectives. HLA-B*27:05 is associated with AS whereas HLA-B*27:09 is not associated. We hypothesized that different interactions with KIR immune receptors could contribute to the difference in disease association between HLA-B*27:05 and HLAB*27:09. Thus, the objective of this study was to compare the formation of b2m-free heavy chain (FHC) including B27 dimers (B272) by HLA-B*27:05 and HLA-B*27:09 and their binding to KIR immunoreceptors. Methods. We studied the formation of HLA-B*27:05 and HLA-B*27:09 heterotrimers and FHC forms including dimers in vitro and in transfected cells. We investigated HLA-B*27:05 and HLA-B*27:09 binding to KIR3DL1, KIR3DL2 and LILRB2 by FACS staining with class I tetramers and by quantifying interactions with KIR3DL2CD3ε-reporter cells and KIR3DL2-expressing NK cells. We also measured KIR expression on peripheral blood NK and CD4 T cells from 18 HLA-B*27:05 AS patients, 8 HLA-B27 negative and 12 HLAB* 27:05+ and HLA-B*27:09+ healthy controls by FACS staining. Results. HLA-B*27:09 formed less B272 and FHC than HLA-B*27:05. HLA-B*27:05-expressing cells stimulated KIR3DL2CD3ε-reporter T cells more effectively. Cells expressing HLA-B*27:05 promoted KIR3DL2+NK cell survival more strongly than HLA-B*27:09. HLA-B*27:05 and HLA-B*27:09 dimer tetramers stained KIR3DL1, KIR3DL2 and LILRB2 equivalently. Increased proportions of NK and CD4 T cells expressed KIR3DL2 in HLA-B*27:05+ AS patients compared with HLA-B*27:05+, HLA-B*27:09+ and HLAB27 - healthy controls. Conclusion. Differences in the formation of FHC ligands for KIR3DL2 by HLA-B*27:05 and HLA-B*27:09 could contribute to the differential association of these alleles with AS.

Original languageEnglish
Pages (from-to)1952-1962
Number of pages11
JournalRheumatology
Volume52
Issue number11
Early online date26 Jun 2013
DOIs
Publication statusPublished - 30 Nov 2013
Externally publishedYes

Keywords

  • B27 homodimer
  • HLA-B*27:05
  • HLA-B*27:09
  • KIR3DL1
  • KIR3DL2
  • Spondyloarthritis

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