Truncated HLA-G isoforms are retained in the endoplasmic reticulum and insufficiently provide HLA-E ligands.
The preferential expression of the non-polymorphic human leukocyte antigen G (HLA-G) on invading extravillous cytotrophoblast cells that are, with the exception of HLA-C and -E, HLA class I negative led to the hypothesis that HLA-G plays a major role in controlling the effector functions of the large granular leukocytes (LGL), a specialized natural killer (NK) cell population present in large numbers in the decidua. Transcription of the HLA-G gene is characterized by extensive alternative splicing producing at least seven potentially membrane bound or secreted isoforms. Except for HLA-G1 and its soluble variant (HLA-G1s), there is still dispute as to whether any of the other isoforms displays a major immunological function. Here we describe that the membrane-bound isoforms HLA-G2, -G3, and G4 as well as the soluble variant of HLA-G2 (HLA-G2s) do not egress the endoplasmic reticulum as determined by Endo H sensitivity assays. Moreover these isoforms seem not to have a major immunological function with respect to NK cell inhibition by providing a ligand for HLA-E, which would allow the interaction of this molecule with the inhibitory CD94/NKG2A NK cell receptor.
Ulbrecht
Matthias
M
Department Biologie II der Ludwig-Maximilians-Universität München, V.H, E.H.W.), Anthropologie und Humangenetik, Munich, Germany. m.ulbrecht@lrz.uni-muenchen.de
Maier
Sabine
S
Hofmeister
Valeska
V
Falk
Christine S
CS
Brooks
Andrew G
AG
McMaster
Michael T
MT
Weiss
Elisabeth H
EH
D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005260:Female; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D007962:Leukocytes / Q000276:immunology*; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology; D014327:Trophoblasts / Q000276:immunology*; D000097625:HLA-E Antigens
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D020033:Protein Isoforms; D000097625:HLA-E Antigens