Molecular Regulatory Mechanisms That Repress Classical HLA Class I Gene Expression in Human Placenta

Abstract

The human major histocompatibility complex (MHC) class I genomic region, located on the short arm of chromosome 6 (6p21.3 position), is composed of about 2000 kb of DNA. Besides pseudogenes and recently evidenced non-HLA class I genes, such as P5, R1, B30 (1), OTF3 (2), and S (3), this region contains both classical and nonclassical HLA class I genes (4). Polymorphic classical HLA-A, -B, -C class I genes are constitutively expressed (or inducible) on most somatic tissues, although at different levels, and play a critical role in cancer and viral immunity. Expression of these genes is developmentally regulated:They are not expressed on the cell surface of either male or female germinal cells (5, 6) or trophoblast cells (7). Current evidence favors repression of their transcription in all subpopulations of trophoblast cells in situ:Neither cytotrophoblast (from both term and first-trimester placentas) nor syncytiotrophoblast expresses these molecules (8). This suggests that such a repression plays a role in the maintenance of pregnancy. In contrast, the nonclassical HLA-E, -F, -G genes have a more restricted somatic tissue distribution, exhibit a low polymorphism, and are not yet associated with a known immunological or other biological function (7). Although nothing is known yet about expression of these genes in germinal cells, it is now clear that cytotrophoblast expresses HLA-G (8), and HLA-E and -F transcripts have been reported in the human placenta (9).