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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

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

In: Rheumatology, 2013, vol. 52, no. 11, p. 1952-1962

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    Titre
    • 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
    Auteur
    • Cauli, Alberto. Rheumatology Unit, Department of Medical Sciences, University of Cagliari, Italy, Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, Headington, Oxford, MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK, Department of Internal Medicine-Oncology, University Hospital Zurich, Zurich, Switzerland, Haematology Unit, Department of Medical Sciences, University of Cagliari, Italy, Oficina de Investigacion Biosanitaria—FICYT, Hospital Universitario Central de Asturias, Oviedo, Department of Immunology, Hospital Universitario Central de Asturias, Oviedo and Fundación Renal Iñigo Alvarez de Toledo, Madrid, Spain.
    • Shaw, Jacqueline. Rheumatology Unit, Department of Medical Sciences, University of Cagliari, Italy, Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, Headington, Oxford, MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK, Department of Internal Medicine-Oncology, University Hospital Zurich, Zurich, Switzerland, Haematology Unit, Department of Medical Sciences, University of Cagliari, Italy, Oficina de Investigacion Biosanitaria—FICYT, Hospital Universitario Central de Asturias, Oviedo, Department of Immunology, Hospital Universitario Central de Asturias, Oviedo and Fundación Renal Iñigo Alvarez de Toledo, Madrid, Spain.
    • Giles, Joanna. Rheumatology Unit, Department of Medical Sciences, University of Cagliari, Italy, Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, Headington, Oxford, MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK, Department of Internal Medicine-Oncology, University Hospital Zurich, Zurich, Switzerland, Haematology Unit, Department of Medical Sciences, University of Cagliari, Italy, Oficina de Investigacion Biosanitaria—FICYT, Hospital Universitario Central de Asturias, Oviedo, Department of Immunology, Hospital Universitario Central de Asturias, Oviedo and Fundación Renal Iñigo Alvarez de Toledo, Madrid, Spain.
    • Hatano, Hiroko. Rheumatology Unit, Department of Medical Sciences, University of Cagliari, Italy, Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, Headington, Oxford, MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK, Department of Internal Medicine-Oncology, University Hospital Zurich, Zurich, Switzerland, Haematology Unit, Department of Medical Sciences, University of Cagliari, Italy, Oficina de Investigacion Biosanitaria—FICYT, Hospital Universitario Central de Asturias, Oviedo, Department of Immunology, Hospital Universitario Central de Asturias, Oviedo and Fundación Renal Iñigo Alvarez de Toledo, Madrid, Spain.
    • Rysnik, Oliwia. Rheumatology Unit, Department of Medical Sciences, University of Cagliari, Italy, Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, Headington, Oxford, MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK, Department of Internal Medicine-Oncology, University Hospital Zurich, Zurich, Switzerland, Haematology Unit, Department of Medical Sciences, University of Cagliari, Italy, Oficina de Investigacion Biosanitaria—FICYT, Hospital Universitario Central de Asturias, Oviedo, Department of Immunology, Hospital Universitario Central de Asturias, Oviedo and Fundación Renal Iñigo Alvarez de Toledo, Madrid, Spain.
    • Payeli, Sravan. Rheumatology Unit, Department of Medical Sciences, University of Cagliari, Italy, Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, Headington, Oxford, MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK, Department of Internal Medicine-Oncology, University Hospital Zurich, Zurich, Switzerland, Haematology Unit, Department of Medical Sciences, University of Cagliari, Italy, Oficina de Investigacion Biosanitaria—FICYT, Hospital Universitario Central de Asturias, Oviedo, Department of Immunology, Hospital Universitario Central de Asturias, Oviedo and Fundación Renal Iñigo Alvarez de Toledo, Madrid, Spain.
    • McHugh, Kirsty. Rheumatology Unit, Department of Medical Sciences, University of Cagliari, Italy, Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, Headington, Oxford, MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK, Department of Internal Medicine-Oncology, University Hospital Zurich, Zurich, Switzerland, Haematology Unit, Department of Medical Sciences, University of Cagliari, Italy, Oficina de Investigacion Biosanitaria—FICYT, Hospital Universitario Central de Asturias, Oviedo, Department of Immunology, Hospital Universitario Central de Asturias, Oviedo and Fundación Renal Iñigo Alvarez de Toledo, Madrid, Spain.
    • Dessole, Grazia. Rheumatology Unit, Department of Medical Sciences, University of Cagliari, Italy, Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, Headington, Oxford, MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK, Department of Internal Medicine-Oncology, University Hospital Zurich, Zurich, Switzerland, Haematology Unit, Department of Medical Sciences, University of Cagliari, Italy, Oficina de Investigacion Biosanitaria—FICYT, Hospital Universitario Central de Asturias, Oviedo, Department of Immunology, Hospital Universitario Central de Asturias, Oviedo and Fundación Renal Iñigo Alvarez de Toledo, Madrid, Spain.
    • Porru, Giovanni. Rheumatology Unit, Department of Medical Sciences, University of Cagliari, Italy, Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, Headington, Oxford, MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK, Department of Internal Medicine-Oncology, University Hospital Zurich, Zurich, Switzerland, Haematology Unit, Department of Medical Sciences, University of Cagliari, Italy, Oficina de Investigacion Biosanitaria—FICYT, Hospital Universitario Central de Asturias, Oviedo, Department of Immunology, Hospital Universitario Central de Asturias, Oviedo and Fundación Renal Iñigo Alvarez de Toledo, Madrid, Spain.
    • Desogus, Elisabetta. Rheumatology Unit, Department of Medical Sciences, University of Cagliari, Italy, Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, Headington, Oxford, MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK, Department of Internal Medicine-Oncology, University Hospital Zurich, Zurich, Switzerland, Haematology Unit, Department of Medical Sciences, University of Cagliari, Italy, Oficina de Investigacion Biosanitaria—FICYT, Hospital Universitario Central de Asturias, Oviedo, Department of Immunology, Hospital Universitario Central de Asturias, Oviedo and Fundación Renal Iñigo Alvarez de Toledo, Madrid, Spain.
    • Fiedler, Sarah. Rheumatology Unit, Department of Medical Sciences, University of Cagliari, Italy, Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, Headington, Oxford, MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK, Department of Internal Medicine-Oncology, University Hospital Zurich, Zurich, Switzerland, Haematology Unit, Department of Medical Sciences, University of Cagliari, Italy, Oficina de Investigacion Biosanitaria—FICYT, Hospital Universitario Central de Asturias, Oviedo, Department of Immunology, Hospital Universitario Central de Asturias, Oviedo and Fundación Renal Iñigo Alvarez de Toledo, Madrid, Spain.
    • Hölper, Soraya. Rheumatology Unit, Department of Medical Sciences, University of Cagliari, Italy, Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, Headington, Oxford, MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK, Department of Internal Medicine-Oncology, University Hospital Zurich, Zurich, Switzerland, Haematology Unit, Department of Medical Sciences, University of Cagliari, Italy, Oficina de Investigacion Biosanitaria—FICYT, Hospital Universitario Central de Asturias, Oviedo, Department of Immunology, Hospital Universitario Central de Asturias, Oviedo and Fundación Renal Iñigo Alvarez de Toledo, Madrid, Spain.
    • Carette, Amanda. Rheumatology Unit, Department of Medical Sciences, University of Cagliari, Italy, Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, Headington, Oxford, MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK, Department of Internal Medicine-Oncology, University Hospital Zurich, Zurich, Switzerland, Haematology Unit, Department of Medical Sciences, University of Cagliari, Italy, Oficina de Investigacion Biosanitaria—FICYT, Hospital Universitario Central de Asturias, Oviedo, Department of Immunology, Hospital Universitario Central de Asturias, Oviedo and Fundación Renal Iñigo Alvarez de Toledo, Madrid, Spain.
    • Blanco-Gelaz, Miguel Angel. Rheumatology Unit, Department of Medical Sciences, University of Cagliari, Italy, Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, Headington, Oxford, MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK, Department of Internal Medicine-Oncology, University Hospital Zurich, Zurich, Switzerland, Haematology Unit, Department of Medical Sciences, University of Cagliari, Italy, Oficina de Investigacion Biosanitaria—FICYT, Hospital Universitario Central de Asturias, Oviedo, Department of Immunology, Hospital Universitario Central de Asturias, Oviedo and Fundación Renal Iñigo Alvarez de Toledo, Madrid, Spain.
    • Vacca, Alessandra. Rheumatology Unit, Department of Medical Sciences, University of Cagliari, Italy, Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, Headington, Oxford, MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK, Department of Internal Medicine-Oncology, University Hospital Zurich, Zurich, Switzerland, Haematology Unit, Department of Medical Sciences, University of Cagliari, Italy, Oficina de Investigacion Biosanitaria—FICYT, Hospital Universitario Central de Asturias, Oviedo, Department of Immunology, Hospital Universitario Central de Asturias, Oviedo and Fundación Renal Iñigo Alvarez de Toledo, Madrid, Spain.
    • Piga, Matteo. Rheumatology Unit, Department of Medical Sciences, University of Cagliari, Italy, Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, Headington, Oxford, MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK, Department of Internal Medicine-Oncology, University Hospital Zurich, Zurich, Switzerland, Haematology Unit, Department of Medical Sciences, University of Cagliari, Italy, Oficina de Investigacion Biosanitaria—FICYT, Hospital Universitario Central de Asturias, Oviedo, Department of Immunology, Hospital Universitario Central de Asturias, Oviedo and Fundación Renal Iñigo Alvarez de Toledo, Madrid, Spain.
    • Ibba, Valentina. Rheumatology Unit, Department of Medical Sciences, University of Cagliari, Italy, Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, Headington, Oxford, MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK, Department of Internal Medicine-Oncology, University Hospital Zurich, Zurich, Switzerland, Haematology Unit, Department of Medical Sciences, University of Cagliari, Italy, Oficina de Investigacion Biosanitaria—FICYT, Hospital Universitario Central de Asturias, Oviedo, Department of Immunology, Hospital Universitario Central de Asturias, Oviedo and Fundación Renal Iñigo Alvarez de Toledo, Madrid, Spain.
    • Garau, Pietro. Rheumatology Unit, Department of Medical Sciences, University of Cagliari, Italy, Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, Headington, Oxford, MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK, Department of Internal Medicine-Oncology, University Hospital Zurich, Zurich, Switzerland, Haematology Unit, Department of Medical Sciences, University of Cagliari, Italy, Oficina de Investigacion Biosanitaria—FICYT, Hospital Universitario Central de Asturias, Oviedo, Department of Immunology, Hospital Universitario Central de Asturias, Oviedo and Fundación Renal Iñigo Alvarez de Toledo, Madrid, Spain.
    • La Nasa, Giorgio. Rheumatology Unit, Department of Medical Sciences, University of Cagliari, Italy, Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, Headington, Oxford, MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK, Department of Internal Medicine-Oncology, University Hospital Zurich, Zurich, Switzerland, Haematology Unit, Department of Medical Sciences, University of Cagliari, Italy, Oficina de Investigacion Biosanitaria—FICYT, Hospital Universitario Central de Asturias, Oviedo, Department of Immunology, Hospital Universitario Central de Asturias, Oviedo and Fundación Renal Iñigo Alvarez de Toledo, Madrid, Spain.
    • López-Larrea, Carlos. Rheumatology Unit, Department of Medical Sciences, University of Cagliari, Italy, Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, Headington, Oxford, MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK, Department of Internal Medicine-Oncology, University Hospital Zurich, Zurich, Switzerland, Haematology Unit, Department of Medical Sciences, University of Cagliari, Italy, Oficina de Investigacion Biosanitaria—FICYT, Hospital Universitario Central de Asturias, Oviedo, Department of Immunology, Hospital Universitario Central de Asturias, Oviedo and Fundación Renal Iñigo Alvarez de Toledo, Madrid, Spain.
    • Mathieu, Alessandro. Rheumatology Unit, Department of Medical Sciences, University of Cagliari, Italy, Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, Headington, Oxford, MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK, Department of Internal Medicine-Oncology, University Hospital Zurich, Zurich, Switzerland, Haematology Unit, Department of Medical Sciences, University of Cagliari, Italy, Oficina de Investigacion Biosanitaria—FICYT, Hospital Universitario Central de Asturias, Oviedo, Department of Immunology, Hospital Universitario Central de Asturias, Oviedo and Fundación Renal Iñigo Alvarez de Toledo, Madrid, Spain.
    • Renner, Christoph. Rheumatology Unit, Department of Medical Sciences, University of Cagliari, Italy, Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, Headington, Oxford, MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK, Department of Internal Medicine-Oncology, University Hospital Zurich, Zurich, Switzerland, Haematology Unit, Department of Medical Sciences, University of Cagliari, Italy, Oficina de Investigacion Biosanitaria—FICYT, Hospital Universitario Central de Asturias, Oviedo, Department of Immunology, Hospital Universitario Central de Asturias, Oviedo and Fundación Renal Iñigo Alvarez de Toledo, Madrid, Spain.
    • Bowness, Paul. Rheumatology Unit, Department of Medical Sciences, University of Cagliari, Italy, Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, Headington, Oxford, MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK, Department of Internal Medicine-Oncology, University Hospital Zurich, Zurich, Switzerland, Haematology Unit, Department of Medical Sciences, University of Cagliari, Italy, Oficina de Investigacion Biosanitaria—FICYT, Hospital Universitario Central de Asturias, Oviedo, Department of Immunology, Hospital Universitario Central de Asturias, Oviedo and Fundación Renal Iñigo Alvarez de Toledo, Madrid, Spain.
    • Kollnberger, Simon. Rheumatology Unit, Department of Medical Sciences, University of Cagliari, Italy, Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, Headington, Oxford, MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK, Department of Internal Medicine-Oncology, University Hospital Zurich, Zurich, Switzerland, Haematology Unit, Department of Medical Sciences, University of Cagliari, Italy, Oficina de Investigacion Biosanitaria—FICYT, Hospital Universitario Central de Asturias, Oviedo, Department of Immunology, Hospital Universitario Central de Asturias, Oviedo and Fundación Renal Iñigo Alvarez de Toledo, Madrid, Spain.
    Type de document
    • Postprint
    Identifiant OAI-PMH
    • oai:doc.rero.ch:295338
    Summary
    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