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

Rheumatology (Oxford). 2013 Nov;52(11):1952-62. doi: 10.1093/rheumatology/ket219. Epub 2013 Jun 26.


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 β2m-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 HLA-B*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 HLA-B27- 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.

Keywords: B27 homodimer; HLA-B*27:05; HLA-B*27:09; KIR3DL1; KIR3DL2; spondyloarthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Survival / immunology
  • Cells, Cultured
  • Coculture Techniques
  • Female
  • Genetic Predisposition to Disease
  • HLA-B27 Antigen / genetics
  • HLA-B27 Antigen / metabolism*
  • Humans
  • Immunoglobulin Heavy Chains / metabolism*
  • Killer Cells, Natural / immunology
  • Ligands
  • Male
  • Middle Aged
  • Receptors, KIR3DL2 / metabolism*
  • Spondylitis, Ankylosing / genetics*
  • Spondylitis, Ankylosing / immunology
  • Spondylitis, Ankylosing / metabolism
  • Transfection


  • HLA-B*27:05 antigen
  • HLA-B*27:09 antigen
  • HLA-B27 Antigen
  • Immunoglobulin Heavy Chains
  • KIR3DL2 protein, human
  • Ligands
  • Receptors, KIR3DL2