TY - JOUR
T1 - Complexes of HLA-G protein on the cell surface are important for leukocyte Ig-like receptor-1 function
AU - Gonen-Gross, Tsufit
AU - Achdout, Hagit
AU - Gazit, Roi
AU - Hanna, Jacob
AU - Mizrahi, Sa'ar
AU - Markel, Gal
AU - Goldman-Wohl, Debra
AU - Yagel, Simcha
AU - Hořejší, Václav
AU - Levy, Ofer
AU - Baniyash, Michal
AU - Mandelboim, Ofer
PY - 2003/8/1
Y1 - 2003/8/1
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=0041845115&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.171.3.1343
DO - 10.4049/jimmunol.171.3.1343
M3 - Article
C2 - 12874224
AN - SCOPUS:0041845115
SN - 0022-1767
VL - 171
SP - 1343
EP - 1351
JO - Journal of Immunology
JF - Journal of Immunology
IS - 3
ER -