Soluble HLA-G generated by proteolytic shedding inhibits NK-mediated cell lysis

Biochem Biophys Res Commun. 2004 Jan 16;313(3):606-11. doi: 10.1016/j.bbrc.2003.11.153.


In contrast to the classical HLA class Ia molecules, the nonclassical HLA-G primary transcript is alternatively spliced to generate several mRNAs that encode four membrane-bound and three soluble isoforms. This study demonstrated that the soluble form of HLA-G can also be generated by metalloproteinase-dependent shedding at post-translational level. These soluble HLA-G1 molecules generated by the cleavage of membrane-bound HLA-G1 associate with beta2-microglobulin and contain bound peptides that are stable at physiological conditions. This report further showed that the soluble HLA-G1 is able to protect HLA class I-negative K562 cells from NK lysis, suggesting that soluble HLA-G could act as an immunoregulator in NK cell recognition and possibly in other immune responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Biotinylation
  • Blotting, Western
  • Cell Membrane / metabolism
  • Electrophoresis, Polyacrylamide Gel
  • HLA Antigens / biosynthesis*
  • HLA-G Antigens
  • Histocompatibility Antigens Class I / biosynthesis*
  • Humans
  • K562 Cells
  • Killer Cells, Natural / metabolism*
  • Metalloproteases / chemistry
  • Peptides / chemistry
  • Precipitin Tests
  • Protein Isoforms
  • Protein Processing, Post-Translational
  • RNA, Messenger / metabolism
  • Temperature
  • Time Factors
  • beta 2-Microglobulin / chemistry


  • HLA Antigens
  • HLA-G Antigens
  • Histocompatibility Antigens Class I
  • Peptides
  • Protein Isoforms
  • RNA, Messenger
  • beta 2-Microglobulin
  • Metalloproteases