The Enigma of Activating Isoforms of ITIM-Bearing Molecules

Abstract

A novel family of inhibitory receptors has been described recently Vivier and Daeron 1997) based on the presence of a conserved immunoreceptor tyrosine-based inhibition motif (ITIM) in the intracytoplasmic portion. The first ITIM-bearing receptors were identified, in cells of hematopoietic origin, as the low affinity receptors for immunoglobulins, FcγRIIB, in B cells (Amigorena et al. 1992; Daëron et al. 1995) and the killer cell Ig-like receptors (KIR) for MHC class I molecules in natural killer (NK) cells (Olcese et al. 1996; Burshtyn et al. 1996). Subsequently, other ITIM-bearing molecules have been described in both hematopoietic cells [PIR-B, (Kubagawa et al. 1997), ILT-2 and -3, (Cella et al. 1997; Samaridis and Colonna 1997), LIR molecules (Borges et al. 1997), MIR molecules, (Wagtmann et al. 1997), CD22, (Sato et al. 1998), and CD72, (Wu et al. 1998)] and nonhematopoietic cells [SIRPα, (Kharitonenkov et al. 1997)]. All these molecules are characterized by the presence of one or more ITIM sequences in their intracytoplasmic portions. This motif is responsible for the transduction of inhibitory signals inside the cells. The ITIM-bearing receptors belong to two families: the immunoglobulin superfamily (IgSF) and the lectin-like superfamily (LSF).