Recombinant Human TIM-4 Fc Chimera (Catalog # 9300-TM)inhibits anti-CD3-induced proliferation of human T cells. The ED50 for thiseffect is 0.15-0.75 μg/mL.
TIM-4 (T cell; immunoglobulin; mucin-4), also known as SMUCKLER, is a 60 kDa member of the TIM family of immune regulating proteins. TIMs are type I transmembrane proteins with one Ig-like V domain and one Ser/Thr-rich mucin domain (1). Mature human TIM-4 consists of a 290 aa extracellular domain (ECD), a 21 aa transmembrane segment, and a 43 aa cytoplasmic tail (2). Structurally, TIM-4 is distinguished from other TIMs by the presence of an RGD motif in its Ig domain and the lack of a site for tyrosine phosphorylation in its cytoplasmic tail. Within the ECD human TIM-4 shares 45% aa sequence identity with mouse and rat TIM-4. TIM-4 is expressed by macrophages and mature dendritic cells but not by lymphocytes (2, 3). It binds specifically to TIM-1 which is also the cellular receptor for hepatitis A virus and has been implicated in the development of asthma (3-5). Among hematopoietic cells, TIM-1 is expressed on activated B and T cells, preferentially in the Th2 subset of CD4+ T cells (3, 6). The interaction of TIM-4 with TIM-1 induces co-stimulatory and hyperproliferative signals in T cells (3). TIM-4 also binds to phosphatidylserine (PS) on the surface of apoptotic cells (7). It enhances the clearance of apoptotic cells including T cells in the contraction phase of immune responses, apoptotic macrophages that accumulate in atherosclerosis, and dying neurons in the brain (7-10). TIM-4 is upregulated on some tumor cells and tumor-associated myeloid cells where it binds Integrin alpha V beta 3, contributes to tumor progression, and inhibits tumor-specific cellular immunity (11, 12).
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