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

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Abstract
With β2-microglobulin− (β2m−) 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 β2m 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 β2m cDNA. After this chimeric cDNA was transfected into R1E/Db cells, β2m-KDEL protein was detectable by an anti-β2m serum within the cells but not at the cell surface. Interestingly, R1E/Db cells transfected with β2m-KDEL were found to express a high level of conformationally correct Db molecules at the cell surface. This observation implies that β2m has a critical and temporal role in the de novo folding of the class I heavy chain. We propose that the critical time for β2m association is when the class I molecule is docked with the transporter associated with antigen processing (TAP) and first interacts with peptide.