PMID- 19136885 OWN - NLM STAT- MEDLINE DCOM- 20090130 LR - 20171116 IS - 1534-6080 (Electronic) IS - 0041-1337 (Linking) VI - 87 IP - 1 DP - 2009 Jan 15 TI - Dimerization of soluble HLA-G by IgG-Fc fragment augments ILT2-mediated inhibition of T-cell alloresponse. PG - 8-15 LID - 10.1097/TP.0b013e31818b6141 [doi] AB - BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: The sHLA-G dimer formed by IgG-Fc fragment shows more inhibitory effects on alloreactive T cells, which may have implications for allotransplantation. FAU - Zhong, Maohua AU - Zhong M AD - Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Weng, Xiufang AU - Weng X FAU - Liang, Zhihui AU - Liang Z FAU - Lu, Shengjun AU - Lu S FAU - Li, Jianan AU - Li J FAU - Chen, Xueling AU - Chen X FAU - Li, Qing AU - Li Q FAU - Sun, Wei AU - Sun W FAU - Song, Yinhong AU - Song Y FAU - Shen, Guanxin AU - Shen G FAU - Wu, Xiongwen AU - Wu X LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Transplantation JT - Transplantation JID - 0132144 RN - 0 (Antigens, CD) RN - 0 (HLA Antigens) RN - 0 (HLA-G Antigens) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Immunoglobulin G) RN - 0 (LILRB1 protein, human) RN - 0 (Leukocyte Immunoglobulin-like Receptor B1) RN - 0 (Receptors, Immunologic) SB - IM MH - Antigens, CD/*immunology MH - Autoimmunity/*immunology MH - Cell Line MH - Cell Proliferation MH - HLA Antigens/*immunology/metabolism MH - HLA-G Antigens MH - Histocompatibility Antigens Class I/*immunology/metabolism MH - Humans MH - Immunoglobulin Fc Fragments/*immunology MH - Immunoglobulin G/*immunology MH - Leukocyte Immunoglobulin-like Receptor B1 MH - Protein Multimerization/*immunology MH - Receptors, Immunologic/*immunology MH - Solubility MH - T-Lymphocytes/cytology/*immunology MH - Up-Regulation/immunology EDAT- 2009/01/13 09:00 MHDA- 2009/01/31 09:00 CRDT- 2009/01/13 09:00 PHST- 2009/01/13 09:00 [entrez] PHST- 2009/01/13 09:00 [pubmed] PHST- 2009/01/31 09:00 [medline] AID - 00007890-200901150-00003 [pii] AID - 10.1097/TP.0b013e31818b6141 [doi] PST - ppublish SO - Transplantation. 2009 Jan 15;87(1):8-15. doi: 10.1097/TP.0b013e31818b6141.