β2-microglobulin with an endoplasmic reticulum retention signal increases the surface expression of folded class I major histocompatibility complex molecules

✍ Scribed by Joyce C. Solheim; Nancy A. Johnson; Beatriz M. Carreno; Wen-Rong Lie; Ted H. Hansen

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Volume: 25
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.1830251104

✦ Synopsis

With P,-microglobulin-( P2m-) cell lines such as RIE/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 P2m 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 P2m cDNA. After this chimeric cDNA was transfected into RIE/Db cells, 0,m-KDEL protein was detectable by an anti-p2m serum within the cells but not at the cell surface. Interestingly, RIE/Db cells transfected with P2m-KDEL were found to express a high level of conformationally correct Db molecules at the cell surface. This observation implies that P2m has a critical and temporal role in the de novo folding of the class I heavy chain. We propose that the critical time for B2m association is when the class I molecule is docked with the transporter associated with antigen processing (TAP) and first interacts with peptide.