Novel proteins associated with MHC class I antigens in cells expressing the adenovirus protein E3/19K.
Assembly of histocompatibility class I antigens (MHC) with beta 2-microglobulin (beta 2m) and peptide takes place in the rough endoplasmic reticulum (ER). At present, it is unclear why peptides generated in the cytosol or ER by proteolysis are not further degraded. Also, it is an open question whether assembly and/or peptide binding is self-instructive 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 their transport to the cell surface. Here we show that immunoprecipitates from human cells that express transfected E3/19K and murine MHC Kd molecules not only contain MHC heavy chain, beta 2m and E3/19K but also two additional proteins with apparent molecular weights of 100 kDa and 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 role as chaperones, we find that glucose starvation induces complex formation between p100/110 and MHC-E3/19K. Most interestingly, p100 and p110 are displaced from the complex by addition of Kd-specific peptides. Therefore, p100 and p110 might be chaperones that promote correct folding of MHC antigens and/or peptide binding to MHC.
Feuerbach
D
D
Hans-Spemann-Laboratory, Max-Planck-Institute for Immunobiology, Freiburg, Germany.
Burgert
H G
HG
D017503:Adenovirus E3 Proteins / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D005947:Glucose / Q000172:deficiency; D006031:Glycosylation; D006183:H-2 Antigens / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D014162:Transfection
D017503:Adenovirus E3 Proteins; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D015395:Histocompatibility Antigens Class I; D008562:Membrane Glycoproteins; D010455:Peptides; D005947:Glucose