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Updated: Aug 25, 2026

Immunopeptidomics: Isolation of Mouse and Human MHC Class I- and II-Associated Peptides for Mass Spectrometry Analysis
Published on: October 15, 2021
Truncated HLA-G isoforms are retained in the endoplasmic reticulum and insufficiently provide HLA-E ligands
Matthias Ulbrecht1, Sabine Maier, Valeska Hofmeister
1Department Biologie II der Ludwig-Maximilians-Universität München, V.H, E.H.W.), Anthropologie und Humangenetik, Munich, Germany. m.ulbrecht@lrz.uni-muenchen.de
Abstract:
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.
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