Dimerization of Soluble HLA-G by IgG-Fc Fragment Augments ILT2-Mediated Inhibition of T-Cell Alloresponse

• DOI: 10.1097/tp.0b013e31818b6141
• Publication Date: 2009-01-09T08:22:48Z
• Authors: Maohua Zhong; Xiufang Weng; Zhihui Liang; Shengjun Lu; Jianan Li; Xueling Chen; Qing Li; Wei Sun; Yinhong Song; Guanxin Shen; Xiongwen Wu
• Keywords: HLA-G Antigens; 0301 basic medicine; T-Lymphocytes; Histocompatibility Antigens Class I; Autoimmunity; Cell Line; Immunoglobulin Fc Fragments; Up-Regulation; 3. Good health; 03 medical and health sciences; Leukocyte Immunoglobulin-like Receptor B1; Solubility; Antigens, CD; HLA Antigens; Immunoglobulin G; Humans; Protein Multimerization; Receptors, Immunologic; Cell Proliferation

Human leukocyte antigen (HLA)-G, a nonclassical HLA class I molecule, induces a wide range of tolerogenic immunological effects by means of interaction with its inhibitory receptors. However, recent studies show that HLA-G dimer formation is essential to bind to its receptors and exhibit its effects.In this study, a soluble divalent HLA-G/IgG molecule (sHLA-G dimer) was constructed. Its inhibitory effect on T-cell alloresponse was studied with mixed lymphocyte reaction in vitro, which was set up by mixing inactivated T1 cells with HLA-mismatched peripheral blood lymphocytes in the presence or absence of the sHLA-G dimer.The results show that sHLA-G dimer inhibits T-cell alloresponse by reducing proliferation of both CD4+ and CD8+ T cells and suppressing generation of alloreactive cytotoxic T lymphocytes at nanomole concentration. The inhibition of the sHLA-G dimer is observed to be more effective than that of sHLA-G monomer. Our results also indicate that sHLA-G dimer up-regulates inhibitory receptor ILT2 on alloreactive CD8+ T cells, which contributes to the significant inhibition on T-cell alloresponse.The sHLA-G dimer formed by IgG-Fc fragment shows more inhibitory effects on alloreactive T cells, which may have implications for allotransplantation.