Tumor-associated calreticulin variants functionally compromise the peptide loading complex and impair its recruitment of MHC-I.

ABSTRACT: Major histocompatibility complex-I-β₂m dimers (MHC-I) bind peptides derived from intracellular proteins, enabling the immune system to distinguish between normal cells and those expressing pathogen-derived or mutant proteins. The peptides bind to MHC-I in the endoplasmic reticulum (ER), and this binding is facilitated by the peptide loading complex (PLC), which contains calreticulin (CRT). CRT associates with MHC-I via a conserved glycan present on MHC-I and recruits it to the PLC for peptide binding. Somatic frameshift mutations in CRT (CRT-FS) drive the proliferation of a subset of myeloproliferative neoplasms, which are chronic blood tumors. All CRT-FS proteins have a C-terminal sequence lacking the normal ER-retention signal and possessing a net negative

SUBMITTER: Arshad N 

PROVIDER: S-EPMC6016473 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature