Mouse TIM-1/KIM-1/HAVCR APC-conjugated Antibody

TIM-1 (T cell-Immunoglobulin-Mucin; also known as KIM-1 or HAVCR) is a 70-80 kDa, type I transmembrane glycoprotein member of the TIM family of immunoglobulin superfamily molecules (1-4). This gene family is involved in the regulation of Th1 and Th2-cell-mediated immunity. In mouse, there are eight known TIM genes (# 1-8) vs. only three genes in human (# 1, 3, and 4) (1, 2). Mouse TIM-1 and -2 are counterparts of human TIM-1 while mouse TIM-5 through 8 have no human counterparts (2). Mouse TIM-1 is synthesized as a 305 amino acid (aa) precursor that contains a 21 aa signal sequence, a 216 aa extracellular domain (ECD), a 21 aa transmembrane segment and a 47 aa cytoplasmic domain (5, 6). The ECD contains one V-type Ig-like domain and a mucin region characterized by multiple T-S-P motifs. The mucin region undergoes extensive O-linked glycosylation. The mouse TIM-1 gene is highly polymorphic and, based on rat, may undergo alternate splicing (4, 6). For instance, HBA mice show a 15 aa deletion in the mucin region that occurs in BALB/c mice (6). This difference is associated with a decreased susceptibility to asthma. Other polymorphisms are also documented (6). In human, TIM-1 is known to circulate as a soluble form. It undergoes constitutive cleavage by an undefined MMP, releasing a 75-85 kDa soluble molecule (5). The same thing might be expected in mouse. The ECD of mouse TIM-1 is 50%, 39% and 80% aa identical to human, canine and rat TIM-1 ECD, respectively. The only two reported ligands for TIM-1 are TIM-4 and the hepatitis A virus (8, 9). However, others are believed to exist, and based on the ligand for TIM-3, one possibility might be an S-type lectin (10). TIM-1 ligation induces T cell proliferation and promotes cytokine production (1, 10). In particular, it induces IL-4 production, and requires the cytoplasmic tyrosine phosphorylation motif (5).