|Detection of NTB‑A/SLAMF6 in Human Lymphocytes by Flow Cytometry. Human whole blood lymphocytes were stained with Sheep Anti-Mouse NTB‑A/SLAMF6 Antigen Affinity‑purified Polyclonal Antibody (Catalog # AF3986, filled histogram) or isotype control antibody (Catalog # 5-001-A, open histogram), followed by NorthernLights™ 637-conjugated Anti-Sheep IgG Secondary Antibody (Catalog # NL011).|
NTB-A, also known as Ly108 and SLAMF6, is a 60 kDa type I transmembrane glycoprotein that belongs to the SLAM subgroup of the CD2 family (1). Mature mouse NTB-A consists of a 209 amino acid (aa) ECD with one Ig-like V-type and one Ig-like C2-type domain, a 23 aa transmembrane segment, and an 89 aa cytoplasmic domain with two immunoreceptor tyrosine-based switch motifs ITSMs (2). Within the ECD, mouse NTB-A shares 48% and 70% aa sequence identity with human and rat NTB-A, respectively. The ECD of mouse NTB-A shares 20%‑34% aa sequence identity with comparable regions of mouse 2B4, BLAME, CD2F-10, CD84, CD229, CRACC, and SLAM. An alternatively spliced isoform diverges after the second ITSM (2). NTB-A is expressed on the surface of NK, T, and B lymphocytes as well as eosinophils (3‑5). It interacts homophilically through weak associations between the Ig-V type domains (5‑7). NTB-A functions as an activating coreceptor on NK and T cells (3, 5, 6, 8). Tyrosine phosphorylation in the membrane proximal ITSM enables specific association with EAT-2, an interaction that is required for NTB-A mediated cytotoxicity of NK cells (9). Phosphorylation-dependent NTB-A association with SAP is required for full production of NK cell IFN-gamma (5, 9). This interaction is independent of EAT-2 binding and appears to involve the membrane distal ITSM (5, 9). NTB-A deficient mice show weakened Th2 responses and elevated levels of neutrophil-derived inflammatory mediators (10). On B cells, NTB-A modulates immunoglobulin class switching and the balance between tolerance and autoimmunity (5, 11). The isoform with the divergent C-terminal tail is overexpressed in B cells from lupus-prone mice (11).
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