Suppression of MHC class I surface expression by calreticulin's P-domain in a calreticulin deficient cell line.
Calreticulin (CRT) is an important chaperone protein, comprising an N-domain, P-domain and C-domain. It is involved in the folding and assembly of multi-component protein complexes in the endoplasmic reticulum, and plays a critical role in MHC class I antigen processing and presentation. To dissect the functional role and molecular basis of individual domains of the protein, we have utilized individual domains to rescue impaired protein assembly in a CRT deficient cell line. Unexpectedly, both P-domain fragment and NP domain of CRT not only failed to rescue defective cell surface expression of MHC class I molecules but further inhibited their appearance on the surface of cells. Formation of the TAP-associated peptide-loading complex and trafficking of the few detectable MHC class I molecules were not significantly impaired. Instead, this further suppression of MHC class I molecules on the cell surface appears due to the complex missing antigenic peptides, the third member of fully assembled MHC class I molecules. Therefore the P-domain of calreticulin appears to play a significant role in antigen presentation by MHC class I molecules.
The Center for Molecular Immunology, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Changzhen
C
Liu
Hongmei
H
Fu
Barry
B
Flutter
Simon J
SJ
Powis
Bin
B
Gao
D000818:Animals; D017951:Antigen Presentation / Q000502:physiology; D037282:Calreticulin / Q000737:chemistry / Q000502:physiology*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D015151:Immunoblotting; D047468:Immunoprecipitation; D051379:Mice; D008810:Mice, Inbred C57BL; D017434:Protein Structure, Tertiary / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D037282:Calreticulin; D015395:Histocompatibility Antigens Class I; D011948:Receptors, Antigen, T-Cell