Boyle, Louise H2; Hermann, Clemens2; Boname, Jessica M2; Porter, Keith M2; Patel, Peysh A2; Burr, Marian L2; Duncan, Lidia M2; Harbour, Michael E2; Rhodes, David A2; Skjødt, Karsten3; Lehner, Paul J2; Trowsdale, John2
1 Department of Cancer and Inflammation Research, Department of Molecular Medicine, Det Sundhedsvidenskabelige Fakultet, SDU2 unknown3 Department of Cancer and Inflammation Research, Department of Molecular Medicine, Det Sundhedsvidenskabelige Fakultet, SDU
Tapasin is an integral component of the peptide-loading complex (PLC) important for efficient peptide loading onto MHC class I molecules. We investigated the function of the tapasin-related protein, TAPBPR. Like tapasin, TAPBPR is widely expressed, IFN-γ-inducible, and binds to MHC class I coupled with β2-microglobulin in the endoplasmic reticulum. In contrast to tapasin, TAPBPR does not bind ERp57 or calreticulin and is not an integral component of the PLC. β2-microglobulin is essential for the association between TAPBPR and MHC class I. However, the association between TAPBPR and MHC class I occurs in the absence of a functional PLC, suggesting peptide is not required. Expression of TAPBPR decreases the rate of MHC class I maturation through the secretory pathway and prolongs the association of MHC class I on the PLC. The TAPBPR:MHC class I complex trafficks through the Golgi apparatus, demonstrating a function of TAPBPR beyond the endoplasmic reticulum/cis-Golgi. The identification of TAPBPR as an additional component of the MHC class I antigen-presentation pathway demonstrates that mechanisms controlling MHC class I expression remain incompletely understood.
National Academy of Sciences. Proceedings, 2013, Vol 110, Issue 9, p. 3465-3470
Antigen Presentation; Calnexin; Calreticulin; Endoplasmic Reticulum; Golgi Apparatus; HEK293 Cells; HLA-A Antigens; HeLa Cells; Histocompatibility Antigens Class I; Humans; Immunoglobulins; Interferon-gamma; Kinetics; Membrane Proteins; Membrane Transport Proteins; Peptides; Protein Binding; Protein Disulfide-Isomerases; Protein Multimerization; Protein Transport; beta 2-Microglobulin