Beta 2-microglobulin with an endoplasmic reticulum retention signal increases the surface expression of folded class I major histocompatibility complex molecules.
With beta 2-microglobulin- (beta 2m-) cell lines such as R1E/Db, the surface expression of class I major histocompatibility complex molecules is greatly impaired, and class I molecules that are on the surface are generally misfolded. To determine whether beta 2m must be continually present with the class I heavy chain for the class I molecule to reach the surface in a folded conformation, a sequence encoding an endoplasmic reticulum (ER) retention signal (KDEL) was attached onto the 3' end of a beta 2m cDNA. After this chimeric cDNA was transfected into R1E/Db cells, beta 2m-KDEL protein was detectable by an anti-beta 2m serum within the cells but not at the cell surface. Interestingly, R1E/Db cells transfected with beta 2m-KDEL were found to express a high level of conformationally correct Db molecules at the cell surface. This observation implies that beta 2m has a critical and temporal role in the de novo folding of the class I heavy chain. We propose that the critical time for beta 2m association is when the class I molecule is docked with the transporter associated with antigen processing (TAP) and first interacts with peptide.
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001483:Base Sequence; D018076:DNA, Complementary / Q000032:analysis; D018870:Endoplasmic Reticulum, Rough / Q000378:metabolism*; D006183:H-2 Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D008223:Lymphoma; D051379:Mice; D008969:Molecular Sequence Data; D021382:Protein Sorting Signals / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D014162:Transfection / Q000235:genetics; D014407:Tumor Cells, Cultured; D001613:beta 2-Microglobulin / Q000378:metabolism / Q000502:physiology*
D000911:Antibodies, Monoclonal; D018076:DNA, Complementary; D006183:H-2 Antigens; D021382:Protein Sorting Signals; D012333:RNA, Messenger; D001613:beta 2-Microglobulin