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J Immunol ; 190(7): 3216-24, 2013 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-23440420

RESUMO

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 ß2-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.


Assuntos
Antígeno HLA-B27/metabolismo , Receptores KIR3DL2/metabolismo , Espondilite Anquilosante/imunologia , Espondilite Anquilosante/metabolismo , Antígenos/imunologia , Linhagem Celular , Sobrevivência Celular/imunologia , Células Cultivadas , Antígeno HLA-A3/imunologia , Antígeno HLA-A3/metabolismo , Antígeno HLA-B27/química , Antígeno HLA-B27/imunologia , Antígeno HLA-B35/imunologia , Antígeno HLA-B35/metabolismo , Antígeno HLA-B7/imunologia , Antígeno HLA-B7/metabolismo , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Interferon gama/biossíntese , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Ligação Proteica , Multimerização Proteica , Receptores KIR3DL2/genética , Receptores KIR3DL2/imunologia , Espondilite Anquilosante/genética , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
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