RecombinantCynomolgus Monkey TIM-4 Fc Chimera(Catalog # 9384-TM) inhibits anti-CD3-induced proliferation of human Tcells. The ED50 for this effect is 0.2-1.2 μg/mL.
TIM-4 (T cell; immunoglobulin; mucin-4), also known as SMUCKLER, is an
approximately 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 (1-3). Sequence alignment with the human TIM-4 shows
that mature cynomolgus monkey TIM-4 has a predicted 280 aa extracellular domain
(ECD), a 21 aa transmembrane segment and a 43 aa cytoplasmic tail. Within the
ECD, cynomolgus monkey TIM-4 shares 87 % and 48 % aa sequence identity with
human and mouse TIM-4, respectively. 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. The mucin domain in
TIM-4 is larger than in TIM-1or TIM-3. TIM-4 is expressed by macrophages and mature
dendritic cells but not by lymphocytes (2, 3). TIM-4 binds specifically to TIM-1
which is also the cellular receptor for the hepatitis A virus, and has been
implicated in the development of asthma (3, 4). Among hematopoietic cells, TIM-1
is expressed on activated B and T cells, preferentially in the Th2 subset of
CD4+ T cells (3, 5). The interaction of TIM-4
TIM-1 induces co-stimulatory and hyperproliferative signals in T cells (3).
Kuchroo, V.K. et al. (2003) Nat. Rev. Immunol. 3:454.
Shakhov, A.N. et al. (2004) Eur. J. Immunol. 34:494.
Meyers, J.H. et al. (2005) Nat. Immunol. 6:455.
McIntire, J.J. et al. (2001) Nat. Immunol. 2:1109.
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