title: Tapasin-related protein TAPBPR is an additional component of the MHC class I presentation pathway.
abstract: 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.
authors: Department of Pathology, Cambridge Institute of Medical Research, University of Cambridge, Cambridge CB2 0XY, United Kingdom. lhb22@cam.ac.uk
authors: Louise H
authors: LH
authors: Boyle
authors: Clemens
authors: C
authors: Hermann
authors: Jessica M
authors: JM
authors: Boname
authors: Keith M
authors: KM
authors: Porter
authors: Peysh A
authors: PA
authors: Patel
authors: Marian L
authors: ML
authors: Burr
authors: Lidia M
authors: LM
authors: Duncan
authors: Michael E
authors: ME
authors: Harbour
authors: David A
authors: DA
authors: Rhodes
authors: Karsten
authors: K
authors: Skjødt
authors: Paul J
authors: PJ
authors: Lehner
authors: John
authors: J
authors: Trowsdale
mesh_terms: D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology*; D037281:Calnexin / Q000378:metabolism; D037282:Calreticulin / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism; D057809:HEK293 Cells; D015234:HLA-A Antigens / Q000378:metabolism; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D007700:Kinetics; D008565:Membrane Proteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism; D010455:Peptides / Q000276:immunology; D011485:Protein Binding / Q000187:drug effects; D019704:Protein Disulfide-Isomerases / Q000378:metabolism; D055503:Protein Multimerization / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D001613:beta 2-Microglobulin / Q000378:metabolism
chemical_list: D037282:Calreticulin; D015234:HLA-A Antigens; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D010455:Peptides; C454688:TAPBPL protein, human; D001613:beta 2-Microglobulin; C107762:tapasin; D037281:Calnexin; D007371:Interferon-gamma; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human
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