Differential expression of MHC class I antigens on the placenta of the rat. A mechanism for the survival of the fetal allograft.
In some mating combinations in rats, there is a maternal antibody response to the maternal antigenic components of the placenta without any previous immunization of the mother. The highest response occurs in the WF (u) female mated to the DA (a) male, and it is against a unique MHC-encoded class I antigen, the Pa antigen, and not against the major allele-specific transplantation antigen of the DA strain, RT1.Aa. The development of mAbs to the Pa and Aa antigens allowed us to localize these antigens on the placenta and to explore the reason for the differential antibody response to them using immunohistochemical and biochemical techniques. Both antibodies reacted with the WF X DA placenta and stained the endovascular and interstitial trophoblast of the decidua, the basal trophoblast, Reichert's membrane, and the yolk sac epithelium, but they did not stain the labyrinthine trophoblast. Blocking studies showed that each antibody reacted with a separate molecule in the placenta. Anti-class II mAbs reactive with the a or u haplotype did not stain the WF X DA, DA X DA, or WF X WF placenta; hence, there are no class II antigens in the placenta. Electron microscopic studies of the semiallogeneic WF X DA placenta using the immunogold technique with both single- and double-labeling showed that only the Pa antigen was expressed on the surface of the basal trophoblast, but that both the Pa and Aa antigens were in the cytoplasm of these cells; neither antigen was found in the labyrinthine trophoblast. By contrast, the placenta from the syngeneic DA X DA mating expressed both the Pa and Aa antigens on the surface of the basal trophoblast as well as in the cytoplasm; neither antigen was found in the labyrinthine trophoblast. These observations were quantified morphometrically using electron photomicrographs of single-labeled tissues. Both the Pa and Aa antigens isolated from the plasma membrane of lymphocytes have heavy chains of 46 kD, but those antigens isolated from the plasma membrane of basal trophoblast cells have heavy chains of 43 kD. Based on densitometric measurements of autoradiographs, the Pa/Aa ratio in the basal trophoblast membrane is 23.5, whereas it is 0.46 in lymphocyte membranes. These studies show that there is differential regulation of the expression of class I antigens on basal trophoblast cells in semiallogeneic pregnancies, but not in syngeneic pregnancies, such that the major allele-specific transplantation antigen is scarcely expressed on the surface of the basal trophoblast.(ABSTRACT TRUNCATED AT 400 WORDS)
Kanbour
A
A
Department of Pathology, University of Pittsburgh, School of Medicine, Pennsylvania 15261.
Ho
H N
HN
Misra
D N
DN
MacPherson
T A
TA
Kunz
H W
HW
Gill
T J
TJ
D000818:Animals; D000911:Antibodies, Monoclonal; D003593:Cytoplasm / Q000276:immunology; D005260:Female; D005865:Gestational Age; D006649:Histocompatibility Antigens / Q000276:immunology*; D015395:Histocompatibility Antigens Class I; D007108:Immune Tolerance; D007150:Immunohistochemistry; D008285:Major Histocompatibility Complex; D008566:Membranes / Q000276:immunology; D010920:Placenta / Q000166:cytology / Q000276:immunology*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000276:immunology*; D011270:Pregnancy, Animal / Q000276:immunology*; D051381:Rats; D014327:Trophoblasts / Q000276:immunology
D000911:Antibodies, Monoclonal; D006649:Histocompatibility Antigens; D015395:Histocompatibility Antigens Class I; D011257:Pregnancy Proteins; C038353:histocompatibility antigens RT, rat; C025625:pregnancy-specific antigen, sheep