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.
Proceedings of the National Academy of Sciences of the United States of America, 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