Placental Expression of HLA Class I Genes

Abstract

This article presents an overview of the more recent data dealing with the constitutive, transcriptional, and translational expression of classical class Ia and nonclassical HLA-E and -G class Ib products in the different trophoblast cell subpopulations that constitute the maternofetal interface during human pregnancy. Of particular interest is the expression of alternatively spliced HLA-G transcriptional isoforms that may be translated in membrane-bound or soluble protein products. Molecular regulatory mechanisms that may control the differential expression of class Ia and class Ib molecules, according to the cell types, state of differentiation, and stages of gestation are also examined. They may operate at the levels of transcription, translation and/or transport of proteins to the cell surface. Functional significance of the absence of detectable cell surface expression of class Ia molecules in all trophoblast cell subpopulations, and of the presence of membrane-bound HLA-G products in extravillous cytotrophoblast cells is finally questioned.

Protein Expression and Peptide Binding Suggest Unique and Interacting Functional Roles for HLA-E, F, and G in Maternal-Placental Immune Recognition

“…3). This confirms the interpretation of Chu et al (8) and stands in contrast to that observed by others (2). At the same time, our analysis showed weak HLA-E expression, consistent with its expression in other cell types (27) that appears to be largely coincident with either the soluble or membrane forms of HLA-G. All results obtained using anti-HLA-E reagent 3D12 were confirmed with reagent 4D12 (data not shown).…”

“…Using Abs that distinguish the soluble and membrane forms of HLA-G, we demonstrated that S ⅐ HLA-G is expressed in all trophoblasts, including syncitiotrophoblasts. This result has been reported (8), but it had been disputed in other studies (2). Although HLA-G is expressed throughout the maternal placental interface, and the S ⅐ HLA-G protein is apparently well distributed in maternal blood at the interface, the peptides bound to HLA-G are apparently quite restricted in number and type.…”

“…Protein expression has been consistently detected on extravillous cytotrophoblast, although detection of expression in the underlying villous cytotrophoblast has yielded contradictory results (2,8). A second nonclassical class I protein, HLA-E, is surface expressed on all cells and tissues that express classical class I and on transfectants that express HLA-G (9), and expression on placental cells has been implicated indirectly (10), whereas a definitive examination of cellular distribution in the placenta remains to be completed.…”

“…Trophoblast cells of the placenta invade deep into the maternal uterine tissue to establish a life-giving connection with the maternal blood supply (1). HLA-G has long been assumed a major factor in this immune accommodation because of its localized expression and because of low levels of allelic polymorphism (2,3). However, little has been elucidated about the expression of the other nonclassical class I molecules, HLA-E and HLA-F, in the placenta, and no studies on peptide bound to any of the nonclassical complexes as they are expressed in the placenta have been reported.…”

An investigation of transmission ratio distortion in the central region of the human MHC

“…Although classical (classes I and II) MHC alleles have been linked to fertility and recurrent spontaneous abortions, 9,10 the trophoblast (that part of the placenta that interfaces mother and foetus) has not been shown to express classical molecules. 11 Together with the proposed long-range linkage disequilibrium (LD) across the MHC, 12 it is possible that associations of HLA genotypes with reproductive outcome could be the result of linked susceptibility genes. This has focused attention elsewhere in the MHC, including the central or class III region, 13 which houses a number of genes involved in both inflammatory responses and the regulation of cell-specific processes.…”