title: KIR3DL2 binds to HLA-B27 dimers and free H chains more strongly than other HLA class I and promotes the expansion of T cells in ankylosing spondylitis.
abstract: The human leukocyte Ag HLA-B27 (B27) is strongly associated with the spondyloarthritides. B27 can be expressed at the cell surface of APC as both classical β2-microglobulin-associated B27 and B27 free H chain forms (FHC), including disulfide-bonded H chain homodimers (termed B27(2)). B27 FHC forms, but not classical B27, bind to KIR3DL2. HLA-A3, which is not associated with spondyloarthritis (SpA), is also a ligand for KIR3DL2. In this study, we show that B27(2) and B27 FHC bind more strongly to KIR3DL2 than other HLA-class I, including HLA-A3. B27(2) tetramers bound KIR3DL2-transfected cells more strongly than HLA-A3. KIR3DL2Fc bound to HLA-B27-transfected cells more strongly than to cells transfected with other HLA-class I. KIR3DL2Fc pulled down multimeric, dimeric, and monomeric FHC from HLA-B27-expressing cell lines. Binding to B27(2) and B27 FHC stimulated greater KIR3DL2 phosphorylation than HLA-A3. B27(2) and B27 FHC stimulated KIR3DL2CD3ε-transduced T cell IL-2 production to a greater extent than control HLA-class I. KIR3DL2 binding to B27 inhibited NK IFN-γ secretion and promoted greater survival of KIR3DL2(+) CD4 T and NK cells than binding to other HLA-class I. KIR3DL2(+) T cells from B27(+) SpA patients proliferated more in response to Ag presented by syngeneic APC than the same T cell subset from healthy and disease controls. Our results suggest that expansion of KIR3DL2-expressing leukocytes observed in B27(+) SpA may be explained by the stronger interaction of KIR3DL2 with B27 FHC.
authors: Nuffield Department of Rheumatological and Musculoskeletal Sciences, Botnar Research Centre, Oxford OX3 7LD, United Kingdom.
authors: Isabel
authors: I
authors: Wong-Baeza
authors: Anna
authors: A
authors: Ridley
authors: Jackie
authors: J
authors: Shaw
authors: Hiroko
authors: H
authors: Hatano
authors: Oliwia
authors: O
authors: Rysnik
authors: Kirsty
authors: K
authors: McHugh
authors: Christopher
authors: C
authors: Piper
authors: Simon
authors: S
authors: Brackenbridge
authors: Ricardo
authors: R
authors: Fernandes
authors: Anthoni
authors: A
authors: Chan
authors: Paul
authors: P
authors: Bowness
authors: Simon
authors: S
authors: Kollnberger
mesh_terms: D000941:Antigens / Q000276:immunology; D002460:Cell Line; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D015791:HLA-A3 Antigen / Q000276:immunology / Q000378:metabolism; D015796:HLA-B27 Antigen / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D015797:HLA-B35 Antigen / Q000276:immunology / Q000378:metabolism; D015793:HLA-B7 Antigen / Q000276:immunology / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D055503:Protein Multimerization; D054347:Receptors, KIR3DL2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013167:Spondylitis, Ankylosing / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D000941:Antigens; D015791:HLA-A3 Antigen; D015796:HLA-B27 Antigen; D015797:HLA-B35 Antigen; D015793:HLA-B7 Antigen; D015395:Histocompatibility Antigens Class I; C515084:KIR3DL2 protein, human; D054347:Receptors, KIR3DL2; D007371:Interferon-gamma