|Detection of KLRG1 in Mouse Splenocytes by Flow Cytometry. Mouse splenocytes were stained with Mouse Anti-Mouse CD161/NK1.1 PE‑conjugated Monoclonal Antibody (Catalog # FAB8319P) and either (A) Rabbit Anti-Mouse KLRG1 APC‑conjugated Monoclonal Antibody (Catalog # FAB6944A) or (B) Normal Rabbit IgG Allophycocyanin Control (Catalog # IC105A). View our protocol for Staining Membrane-associated Proteins.|
KLRG1 (Killer cell Lectin-like Receptor G1), also called MAFA (Mast cell Function Associated), is an inhibitory type II transmembrane glycoprotein of the C-type lectin family, designated CLEC15A (1). Mature mouse KLRG1 consists of a 33 amino acid (aa) cytoplasmic domain with one Immunoreceptor Tyrosine-based Inhibitory Motif (ITIM), a 23 aa transmembrane segment, and a 132 aa extracellular domain (ECD) with one C-type lectin domain (CTLD) (2). Within the ECD, mouse KLRG1 shares 57% and 80% aa sequence identity with human and rat KLRG1, respectively. Alternate splicing generates additional isoforms of mouse KLRG1 that lack either the CTLD or the CTLD, transmembrane segment, and a portion of the cytoplasmic domain (3). KLRG1 is expressed as a 30-40 kDa N-glycosylated molecule that forms disulfide-linked homodimers, trimers, and tetramers (4, 5). It is expressed on subpopulations of CD8+, CD4+, regulatory, and gamma/delta T cells as well as on NK cells (2, 4, 6-8). KLRG1 is expressed on T cells found in cord blood, but it is down-regulated postnatally and is subsequently re-expressed on antigen-exposed T cells (7, 9). It is expressed by a greater proportion of CD8+ T cells in the elderly and by virus-specific CD8+ T cells during chronic virus infection (10-12). KLRG1 binds to E-, N-, and R-Cadherins, triggering ITIM-dependent KLRG1 signaling and inhibition of T cell activation (5, 13, 14). The response is bi‑directional, as KLRG1 binding to E-Cadherin on dendritic cells (DC) can induce an anti-inflammatory DC phenotype (increased IL-10 production and decreased IL-6 and TNF-alpha production) (15).