Trem-like transcript 2 protein (TLT-2; also TREML2) is a 33 kDa (unglycosylated) type I transmembrane cell surface receptor and member of the Trem family of receptor proteins.?Human TLT-2 is synthesized as a 321 amino acid (aa) precursor that contains an 18 aa signal sequence, a 250 aa extracellular domain (ECD), a 21 aa transmembrane segment, and a 32 aa cytoplasmic tail (SwissProt?#?Q5T2D2). Within the ECD are an Ig-like V-type domain (aa 20???121) and one potential site of N-linked glycosylation.?Mature human TLT-2 shares 49% aa sequence identity with mature mouse TLT-2. Cell surface expression of TLT-2 is seen for most of the B and myeloid cell lines (1???2). TLT-2 is also expressed constitutively on CD8+ T cells and induced on CD4+ T?cells after activation (2). TLT-2 plays a role in the innate and adaptive immune responses.?In 2008, Hashiguchi et al. discovered that the B7 family member B7-H3, which also plays important roles in immune responses, specifically bound to TLT-2.?According to their research, stimulation with B7-H3 transfectants preferentially up-regulated the proliferation and IFN-gamma production on CD8+ T?cells (2).?Also, transduction of TLT-2 into T?cells resulted in enhanced IL-2 and IFN-gamma production via interactions with B7-H3, and blockade of the B7?H3:TLT?2 pathway with mAb against B7-H3 or TLT-2 efficiently inhibited contact hypersensitivity responses (2).?In 2009, however, Leitner et al. extensively analyzed interaction of B7-H3 with TLT-2 and found no evidence for such an interaction (3).