Complexes of HLA-G protein on the cell surface are important for leukocyte Ig-like receptor-1 function

Tsufit Gonen-Gross, Hagit Achdout, Roi Gazit, Jacob Hanna, Sa'ar Mizrahi, Gal Markel, Debra Goldman-Wohl, Simcha Yagel, Václav Hořejší, Ofer Levy, Michal Baniyash, Ofer Mandelboim

Research output: Contribution to journalArticlepeer-review

125 Scopus citations


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.

Original languageEnglish
Pages (from-to)1343-1351
Number of pages9
JournalJournal of Immunology
Issue number3
StatePublished - 1 Aug 2003
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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