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

被引：53

作者：

Cauli, Alberto ^{[1
]}

Shaw, Jacqueline ^{[2
]}

Giles, Joanna ^{[3
]}

Hatano, Hiroko ^{[2
]}

Rysnik, Oliwia ^{[2
]}

Payeli, Sravan ^{[4
]}

McHugh, Kirsty ^{[3
]}

Dessole, Grazia ^{[1
]}

Porru, Giovanni ^{[1
]}

Desogus, Elisabetta ^{[5
]}

Fiedler, Sarah ^{[3
]}

Holper, Soraya ^{[3
]}

Carette, Amanda ^{[3
]}

Blanco-Gelaz, Miguel Angel

Vacca, Alessandra ^{[1
]}

Piga, Matteo ^{[1
]}

Ibba, Valentina ^{[1
]}

Garau, Pietro ^{[1
]}

La Nasa, Giorgio ^{[5
]}

Lopez-Larrea, Carlos

Mathieu, Alessandro ^{[1
]}

Renner, Christoph ^{[4
]}

Bowness, Paul ^{[2
,3
]}

Kollnberger, Simon ^{[2
]}

机构：

[1] Univ Cagliari, Rheumatol Unit, Dept Med Sci, I-09124 Cagliari, Italy

[2] Univ Oxford, Botnar Res Ctr, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Oxford OX3 7LD, England

[3] John Radcliffe Hosp, Weatherall Inst Mol Med, MRC Human Immunol Unit, Oxford OX3 9DU, England

[4] Univ Zurich Hosp, Dept Internal Med Oncol, CH-8091 Zurich, Switzerland

[5] Univ Cagliari, Dept Med Sci, Haematol Unit, I-09124 Cagliari, Italy

来源：

RHEUMATOLOGY | 2013年 / 52卷 / 11期

基金：

日本学术振兴会;

关键词：

spondyloarthritis; HLA-B*27:05; HLA-B*27:09; B27; homodimer; KIR3DL1; KIR3DL2; HLA CLASS-I; FREE H CHAINS; ANKYLOSING-SPONDYLITIS; HLA-B27; HOMODIMERS; SELF-PEPTIDE; RECEPTOR B2; T-CELLS; SUBTYPES; SPONDYLOARTHRITIS; SPONDYLARTHRITIS;

D O I：

10.1093/rheumatology/ket219

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

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 KIR3DL2CD3 epsilon-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 B27(2) and FHC than HLA-B*27:05. HLA-B*27:05-expressing cells stimulated KIR3DL2CD3 epsilon-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.

引用

页码：1952 / 1962

页数：11

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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

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