|Detection of KLRG1 in Mouse Splenocytes by Flow Cytometry. Mouse splenocytes were stained with Mouse Anti-Mouse CD161/NK1.1 APC‑conjugated Monoclonal Antibody (Catalog # FAB8319A) and either (A) Rabbit Anti-Mouse KLRG1 Alexa Fluor® 488‑conjugated Monoclonal Antibody (Catalog # FAB6944G) or (B) Normal Rabbit IgG Alexa Fluor 488 Control (Catalog # IC105G). 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).