KLRC1
Description
The KLRC1 (killer cell lectin like receptor C1) is a protein-coding gene located on chromosome 12.
KLRC1 is a gene that encodes a protein known as Killer cell lectin-like receptor C1. This protein is a type II transmembrane receptor that plays a crucial role in regulating immune responses.
KLRC1 is an immune inhibitory receptor that plays a critical role in self-nonself discrimination. It forms a complex with KLRD1 on cytotoxic and regulatory lymphocytes, recognizing the non-classical MHC class Ib molecule HLA-E loaded with self-peptides derived from the signal sequences of classical MHC class Ia molecules. This allows cytotoxic cells to monitor MHC class I expression in healthy cells and tolerate self. Upon binding HLA-E-peptide, KLRC1 transmits inhibitory signals through two ITIMs (immunoreceptor tyrosine-based inhibition motifs), recruiting INPP5D/SHP-1 and INPPL1/SHP-2 tyrosine phosphatases to oppose activating receptor signals. KLRC1 is a key inhibitory receptor on NK cells, regulating their activation and effector functions. It also counteracts T cell receptor signaling on memory/effector CD8-positive T cells, preventing autoimmunity. In intraepithelial CD8-positive gamma-delta regulatory T cells, KLRC1 triggers TGFB1 secretion, limiting cytotoxic programming of intraepithelial CD8-positive alpha-beta T cells and distinguishing harmless from pathogenic antigens. In HLA-E-rich tumor microenvironments, KLRC1 acts as an immune inhibitory checkpoint, potentially contributing to NK cell and tumor-specific T cell exhaustion.
KLRC1 is also known as CD159A, NKG2, NKG2A.
