HLAG

HLAG commonly refers to the human leukocyte antigen G gene, usually written HLA-G. It encodes the HLA-G protein, a non-classical major histocompatibility complex (MHC) class I molecule. The HLA-G gene is located on chromosome 6p21.3 within the MHC region. Compared with classical HLA class I genes, HLA-G shows limited polymorphism and a restricted pattern of tissue expression, being highly expressed by placental trophoblasts and detectable at lower levels in several immune-privileged sites.

HLA-G exists in multiple isoforms produced by alternative splicing. There are four membrane-bound isoforms (HLA-G1 through HLA-G4) and three soluble isoforms (HLA-G5 through HLA-G7). All HLA-G heavy chains pair with β2-microglobulin to form functional molecules, and the isoforms differ in their transmembrane and cytoplasmic portions as well as in their ability to be shed into bodily fluids. The protein contains the typical MHC class I domains (α1, α2, α3) that form the antigen-presenting surface, though its peptide-binding repertoire is more limited than that of classical HLA molecules.

Functionally, HLA-G interacts with inhibitory receptors such as ILT2 (LILRB1) and ILT4 (LILRB2) on natural killer cells, T cells, B cells, and dendritic cells, delivering inhibitory signals that dampen immune cytotoxicity and alloreactivity. Some interactions with KIR family receptors, including KIR2DL4, have also been described. In pregnancy, placental expression of HLA-G contributes to maternal–fetal tolerance and successful gestation; in other contexts, HLA-G expression can influence transplant tolerance and tumor immune escape.

Regulation of HLAG expression involves transcriptional and post-transcriptional controls, including cytokines and polymorphisms in promoter and 3' untranslated regions that affect mRNA stability and isoform production.