Complexes of HLA-G protein on the cell surface are important for leukocyte Ig-like receptor-1 function
Complexes of HLA-G protein on the cell surface are important for leukocyte Ig-like receptor-1 function
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DOI：
10.4049/jimmunol.171.3.1343
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发表时间：
2003-08-01
影响因子：
4.4
通讯作者：
Mandelboim, O
中科院分区：
文献类型：
--
作者：
Gonen-Gross, T;Achdout, H;Mandelboim, O
非经典I类MHC分子HLA-G在妊娠期间在母胎界面的胞外滋养细胞上选择性表达。HLA-G可通过与抑制性NK细胞受体白细胞igg样受体-1 （LIR-1）相互作用抑制NK细胞介导的杀伤。将HLA-G分子序列与其他I类MHC蛋白的序列进行比较，发现位于42和147位的两个独特的半胱氨酸残基。突变这些半胱氨酸残基导致LIR-1 Ig结合显著降低。因此，突变的HLA-G在抑制NK杀伤和RBL/ lr -1诱导的血清素释放方面效果较差。免疫沉淀实验证明半胱氨酸残基参与了细胞表面HLA-G蛋白低聚物的形成。位于42号位置的半胱氨酸残基对这些复合物的表达至关重要。这些寡聚物在I类MHC蛋白中是独特的，可能与LIR-1结合的频率增加，导致LIR-1的抑制功能增强，NK细胞的杀伤功能受损。
The nonclassical class I MHC molecule HLA-G is selectively expressed on extravillous cytotrophoblast cells at the maternal-fetal interface during pregnancy. HLA-G can inhibit the killing mediated by NK cells via interaction with the inhibitory NK cell receptor, leukocyte Ig-like receptor-1 (LIR-1). Comparison of the sequence of the HLA-G molecule to other class I MHC proteins revealed two unique cysteine residues located in positions 42 and 147. Mutating these cysteine residues resulted in a dramatic decrease in LIR-1 Ig binding. Accordingly, the mutated HLA-G transfectants were less effective in the inhibition of NK killing and RBL/LIR-1 induced serotonin release. Immunoprecipitation experiments demonstrated the involvement of the cysteine residues in the formation of HLA-G protein oligomers on the cell surface. The cysteine residue located at position 42 is shown to be critical for the expression of such complexes. These oligomers, unique among the class I MHC proteins, probably bind to LIR-1 with increased avidity, resulting in an enhanced inhibitory function of LIR-1 and an impaired killing function of NK cells.