Calreticulin maintains the low threshold of peptide required for efficient antigen presentation.
Calreticulin (CRT) plays a critical role in MHC class I antigen processing and elicits peptide-specific CD8(+) T cell responses against tumours when administered with peptides. However, how CRT contributes to class I antigen processing and the mechanism of its adjuvant effect in anti-tumour responses, remain to be elucidated. Here we show that reduced class I expression in CRT deficient cells can be restored by the direct delivery of peptides into the ER or by incubation at low temperature. CRT deficient cells exhibited a TAP-deficient phenotype in terms of class I assembly, without loss of TAP expression or functionality. Furthermore, a higher concentration of antigen in the cytosol is required for specific T cell stimulation, suggesting that CRT has a functional role in the maintenance of the low peptide concentration threshold required in the ER for efficient antigen presentation. In the absence of CRT, ERp57 is up-regulated, which indicates that they collaborate with each other in class I antigen processing.
Fu
Hongmei
H
Rheumatology Unit, UCL Institute of Child Health, University College London, London, UK.
Liu
Changzhen
C
Flutter
Barry
B
Tao
Hua
H
Gao
Bin
B
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D000950:Antigens, Ly / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes; D064032:Calbindin 2; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D009363:Neoplasm Proteins / Q000276:immunology; D009369:Neoplasms / Q000276:immunology; D010455:Peptides / Q000276:immunology*; D019704:Protein Disulfide-Isomerases / Q000235:genetics / Q000276:immunology; D064030:S100 Calcium Binding Protein G / Q000235:genetics / Q000276:immunology*
D000950:Antigens, Ly; D064032:Calbindin 2; D015395:Histocompatibility Antigens Class I; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D010455:Peptides; D064030:S100 Calcium Binding Protein G; C513195:Pdia3 protein, mouse; D019704:Protein Disulfide-Isomerases