Defective assembly of class I major histocompatibility complex molecules in an embryonic cell line.
Developmentally regulated expression of the products of the major histocompatibility complex (MHC) is thought to play a key role in maternal tolerance of the fetal allograft. Here we analyze a cell line (EE2H3), derived from early post-implantation-stage mouse embryos, that is defective for MHC class I assembly. To follow expression of a single well-defined class I product, we introduced the H-2Dd gene under control of the human beta-actin promoter. We found that the transfected EE2H3 cells expressed abundant levels of H-2Dd heavy chains and beta 2-microglobulin protein, but only small amounts of H-2Dd surface protein. Surface expression was rescued by the addition of an appropriate antigenic peptide, or by culturing the cells at low temperature. The phenotype exhibited by EE2H3 is thus remarkably similar to that described for class I-negative somatic cell variants selected using antibodies and complement. However, a striking difference was that surface expression in H-2Dd-transfected EE2H3 cells was markedly enhanced in response to treatment with interferon. Thus, we have identified a novel class I assembly-defective cell line. Considering that EE2H3 was established from primary cultures of mouse embryo cells without immunoselection, and is therefore likely to represent a cell population normally present in post-implantation-stage embryos, these findings raise the possibility that expression of class I surface antigens during early development may in part be controlled post-translationally at the level of MHC class I assembly.
Bikoff
E K
EK
Department of Obstetrics, Gynecology, and Reproductive Sciences, Mount Sinai School of Medicine, New York, NY 10029.
Otten
G R
GR
Robertson
E J
EJ
D000818:Animals; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006183:H-2 Antigens / Q000096:biosynthesis*; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis; D066298:In Vitro Techniques; D007372:Interferons / Q000494:pharmacology; D051379:Mice; D014176:Protein Biosynthesis / Q000187:drug effects; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000032:analysis; D014162:Transfection; D001613:beta 2-Microglobulin / Q000096:biosynthesis
D006183:H-2 Antigens; D007143:Immunoglobulin Heavy Chains; D012333:RNA, Messenger; D001613:beta 2-Microglobulin; D007372:Interferons