PMID- 12874224 OWN - NLM STAT- MEDLINE DCOM- 20031107 LR - 20220224 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 171 IP - 3 DP - 2003 Aug 1 TI - Complexes of HLA-G protein on the cell surface are important for leukocyte Ig-like receptor-1 function. PG - 1343-51 AB - 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. FAU - Gonen-Gross, Tsufit AU - Gonen-Gross T AD - Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical School, Jerusalem, Israel. FAU - Achdout, Hagit AU - Achdout H FAU - Gazit, Roi AU - Gazit R FAU - Hanna, Jacob AU - Hanna J FAU - Mizrahi, Sa'ar AU - Mizrahi S FAU - Markel, Gal AU - Markel G FAU - Goldman-Wohl, Debra AU - Goldman-Wohl D FAU - Yagel, Simcha AU - Yagel S FAU - Horejsi, Vaclav AU - Horejsi V FAU - Levy, Ofer AU - Levy O FAU - Baniyash, Michal AU - Baniyash M FAU - Mandelboim, Ofer AU - Mandelboim O LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Antigens, CD) RN - 0 (HLA Antigens) RN - 0 (HLA-G Antigens) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (LILRB1 protein, human) RN - 0 (Leukocyte Immunoglobulin-like Receptor B1) RN - 0 (Macromolecular Substances) RN - 0 (Membrane Glycoproteins) RN - 0 (Receptors, Immunologic) RN - K848JZ4886 (Cysteine) SB - IM MH - Amino Acid Sequence MH - Animals MH - Antigens, CD/metabolism/*physiology MH - Binding, Competitive/genetics/immunology MH - Cell Line, Transformed MH - Cysteine/genetics/physiology MH - Cytotoxicity, Immunologic/genetics MH - Decidua/cytology/immunology MH - Down-Regulation/genetics/immunology MH - Female MH - HLA Antigens/biosynthesis/genetics/metabolism/*physiology MH - HLA-G Antigens MH - Histocompatibility Antigens Class I/biosynthesis/genetics/metabolism/*physiology MH - Humans MH - Leukocyte Immunoglobulin-like Receptor B1 MH - Macromolecular Substances MH - Membrane Glycoproteins/biosynthesis/genetics/metabolism/*physiology MH - Molecular Sequence Data MH - Mutagenesis, Site-Directed MH - Protein Binding/genetics/immunology MH - Rats MH - Receptors, Immunologic/antagonists & inhibitors/metabolism/*physiology MH - Transfection MH - Tumor Cells, Cultured EDAT- 2003/07/23 05:00 MHDA- 2003/11/08 05:00 CRDT- 2003/07/23 05:00 PHST- 2003/07/23 05:00 [pubmed] PHST- 2003/11/08 05:00 [medline] PHST- 2003/07/23 05:00 [entrez] AID - 10.4049/jimmunol.171.3.1343 [doi] PST - ppublish SO - J Immunol. 2003 Aug 1;171(3):1343-51. doi: 10.4049/jimmunol.171.3.1343.