Localization of paternal H-2K antigens on murine trophoblast cells in vivo.

Abstract

The fetoplacental unit resulting from an allogeneic mating is a natural allograft that is not rejected by the otherwise immunocompetent mother (1, 2). Of the various hypotheses proposed to explain this phenomenon, the possible absence of major histocompatibility antigens from the surface of the fetally derived trophoblast cells which lie at the fetomaternal interface has been the focus of extensive investigation (3)(4)(5)(6)(7)(8)(9)(10)(11).We have recently demonstrated (10) the presence of H-2K and D antigens of both maternal and paternal haplotypes on the surface of murine trophoblast cells in suspensions of collagenase-dispersed placentae from 9 to 18 d of gestation, using monospecific antisera and a highly sensitive radioautographic technique. The antigen density on 19-and 14-d trophoblasts was comparable to that on adult F1 thymocytes and a further 50% increase was observed at term. However, the question still remained as to whether these antigens are expressed in situ, and if so, whether they are detectable on the face of trophoblast cells that line the maternal sinusoids in vivo, and thus accessible to the maternal circulation. Studies by Kirby and Cowell (11) and Parr et al. (12) have demonstrated that H-2 antigens may be sequestered on one aspect of certain cells, e.g., the epithelial cells of the small intestine and the endoderm cells of the yolk sac.This study was designed to examine the presence of H-2K antigens on the sinusoidal surface of murine trophoblast cells in vivo, without destroying the architecture of the intact placenta. The use of a radioautographic technique, after an in vivo perfusion with radioiodinated antibodies via individual placental branches of the uterine artery, ensured high levels of sensitivity. High levels of specificity were provided by the use of monoclonal antibodies raised against the H-2K antigens of the paternal haplotype. The visualization and quantitation of radioautographic silver grains on morphologically identified trophoblast cells allowed good resolution. The results revealed significant levels of H-2K antigens of the paternal haplotype on the sinusoidal face of mouse trophoblast cells in the labyrinthine region of placentae derived from allogeneic matings. Materials and MethodsMice. C57BL/6J females were mated with CBA/J or C57BL/6J males (6-12 wk of age; The Jackson Laboratory, Bar Harbor, ME) and provided allogeneic and syngeneic placentae,

Paternal MHC expression on mouse trophoblast affects uterine vascularization and fetal growth

“…Taking advantage of intercrosses between mouse strains with defined H2 haplotypes, we further demonstrate presence of the paternal H2-K allele on trophoblast giant cells. These results correlate with previous reports of the detection of MHC transcripts in preimplantation embryos and trophoblast samples from E7.5 onward (27,28) and presence of paternal H2-K antigens on early trophoblast and on the sinusoidal face of mouse labyrinthine trophoblast cells in the lategestation placenta (25,26,35). In contrast to the typical coexpression of H2-K and H2-D on the surface of virtually all nucleated cells, however, we find that mouse trophoblast expresses only one predominant classical polymorphic MHC molecule, H2-K.…”

“…However, a key question is whether mouse trophoblast expresses MHC class I antigens that could functionally interact with uNK cell receptors. Several studies have suggested the presence of H2 molecules, which represent the main group of MHC class I antigens in the mouse, either at the RNA level or by antisera binding (25)(26)(27)(28)(29). What is still unknown is which H2 loci are expressed as proteins, whether they are displayed at the cell surface, and on which trophoblast subsets they are found.…”

Control of H-2 antigen and beta 2-microglobulin gene expression in mouse trophoblast cell clones.

“…The expression of the major histocompatibility complex, particularly of H-2 antigens, on the trophoblast has long been of interest because of an apparent immunological paradox in pregnancy in which the semi-allogeneic fetus fails to elicit immunological rejection in the pregnant host (3)(4)(5)(6)(7). Another interesting observation is the finding that, when the mouse placenta was separated into its two major components, spongiotrophoblasts and labyrinthine trophoblasts, H-2 antigens were detected only on the spongiotrophoblasts (8).…”

“…Hybridization with a 32P-labeled cloned /32-microglobulin cDNA probe (24) detected major transcripts of =1,250 and ='1,050 bases (Fig. 4B) 4) and C57BL/ 6 trophoblast cells (lanes [6][7][8][9] were analyzed by immunoprecipitation with anti-H-2b alloantiserum (lanes 1 and 6), normal mouse serum (lanes 2 and 7), rabbit anti-182-microglobulin serum (lanes 3 and 8), and normal rabbit serum (lanes 4 and 9) and electrophoresis on a 12% NaDodSO4/polyacrylamide gel. (28,29).…”

“…Two H-2-specific cDNA probes were used, one derived from the highly conserved third external domain including amino acids 151-236 (Fig. 4A, lanes 1-4) and the other, from the 3' noncoding region unique to one subclass of H-2 transcripts (lanes [5][6][7][8]. Hybridization with the cDNA probe to total liver RNA from BALB/c (lanes 1 and 5) and SWR (lanes 2 and 6) mouse strains detected a transcript of =1,800 bases (25).…”