Soluble HLA-G generated by proteolytic shedding inhibits NK-mediated cell lysis.
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.
Park
Gyu Man
GM
College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
Lee
Sunray
S
Park
Boyoun
B
Kim
Eunkyung
E
Shin
Jinwook
J
Cho
Kwangmin
K
Ahn
Kwangseog
K
D017398:Alternative Splicing; D019921:Biotinylation; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006680:HLA Antigens / Q000096:biosynthesis*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006801:Humans; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000378:metabolism*; D045726:Metalloproteases / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D011233:Precipitin Tests; D020033:Protein Isoforms; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism; D013696:Temperature; D013997:Time Factors; D001613:beta 2-Microglobulin / Q000737:chemistry
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D020033:Protein Isoforms; D012333:RNA, Messenger; D001613:beta 2-Microglobulin; D045726:Metalloproteases