Dimerization of soluble HLA-G by IgG-Fc fragment augments ILT2-mediated inhibition of T-cell alloresponse.
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.


CONCLUSIONS
The sHLA-G dimer formed by IgG-Fc fragment shows more inhibitory effects on alloreactive T cells, which may have implications for allotransplantation.
Zhong
Maohua
M
Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Weng
Xiufang
X
Liang
Zhihui
Z
Lu
Shengjun
S
Li
Jianan
J
Chen
Xueling
X
Li
Qing
Q
Sun
Wei
W
Song
Yinhong
Y
Shen
Guanxin
G
Wu
Xiongwen
X
D015703:Antigens, CD / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D002460:Cell Line; D049109:Cell Proliferation; D006680:HLA Antigens / Q000276:immunology* / Q000378:metabolism; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D055503:Protein Multimerization / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology*; D012995:Solubility; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
D015703:Antigens, CD; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D011971:Receptors, Immunologic