NOVEL PROTEINS ASSOCIATED WITH MHC CLASS-I ANTIGENS IN CELLS EXPRESSING THE ADENOVIRUS PROTEIN E3 19K/

Assembly of histocompatibility class I antigens (MHC) with beta2-micro globulin (beta2m) and peptide takes place in the rough endoplasmic ret iculum (ER). At present, it is unclear why peptides generated in the c ytosol or ER by proteolysis are not further degraded. Also, it is an o pen question whether assembly and/or peptide binding is self-instructi ve or is promoted by additional molecules, for example, chaperones. We previously demonstrated that the adenovirus glycoprotein E3/19K binds to human and some mouse MHC molecules in the ER, interfering with the ir transport to the cell surface. Here we show that immunoprecipitates from human cells that express transfected E3/19K and murine MHC K(d) molecules not only contain MHC heavy chain, beta2m and E3/19K but also two additional proteins with apparent molecular weights of 100 kDa an d 110 kDa. Biochemical characterization of these proteins, designated p100 and p110, demonstrates that they are transmembrane glycoproteins with a similar if not identical protein backbone. Consistent with a ro le as chaperones, we find that glucose starvation induces complex form ation between p100/110 and MHC-E3/19K. Most interestingly, p100 and p1 10 are displaced from the complex by addition of K(d)-specific peptide s. Therefore, p100 and p110 might be chaperones that promote correct f olding of MHC antigens and/or peptide binding to MHC.