¦Â2-Microglobulin-free HLA-G activates natural killer cells by increasing cytotoxicity and proinflammatory cytokine production

详细信息    查看全文

• 作者：Longmei Zhao^a ; Bhamini Purandare^a ; Jian Zhang^b ; ^c ; Basil M. Hantash^a ; ^b ; ^{basil@escapetherapeutics.com}
• 关键词：HLA ; human leukocyte antigen ; ¦Â2m ; ¦Â2-microglobulin ; NK ; natural killer ; DCs ; dendritic cells ; ILT ; immunoglobulin-like transcript ; KIR ; killer immunoglobulin receptor ; IFN-¦Â ; interferon ¦Â ; MHC ; major histocompatibility complex ; mAbs ; monoclonal antib
• 刊名：Human Immunology
• 出版年：2013
• 出版时间：April, 2013
• 年：2013
• 卷：74
• 期：4
• 页码：417-424
• 全文大小：1266 K

文摘

Human leukocyte antigen-G (HLA-G) is a nonclassical HLA class-I molecule and plays a role in tissue specific immunoregulation. Many studies have addressed functional aspects of ¦Â2-microglobulin (¦Â2m)-associated HLA-G1. ¦Â2m-free HLA-G has been found in human placental cytotrophoblasts and pancreatic ¦Â cells although its function remains unclear. In the present study, we investigated the function of ¦Â2m-free HLA-G by transfecting HLA-G1 and -G3 into human ¦Â2m deficient rat pancreatic ¦Â cell carcinoma (BRIN-BD11) cells. RT-PCR and western blots studies confirmed high expression of HLA-G1 and -G3 in -G1 and -G3 transfectants, respectively. HLA-G1 and -G3 were detected mainly in intracellular compartments of BRIN-BD11 transductants by confocal fluorescent microscopy and flow cytometry. Functional analysis revealed that ¦Â2m-free HLA-G promoted xenogeneic cytotoxic lysis of BRIN-BD11 cells by natural killer (NK) cells and increased production of IL-1¦Â, TNF-¦Á, and IFN-¦Ã. Stimulation of cytotoxic lysis was impaired by blocking the MAPK and DNA-PKcs pathways in NK cells. Importantly, treatment with 33mAb, a KLR2DL4 receptor agonist, induced NK-mediated cytotoxic lysis of BRIN-BD11 cells transfected with a mock vector. Our data suggest that ¦Â2m-free HLA-G activates NK cells via engagement of KLR2DL4 receptors.