A Novel Family of Inhibitory Receptors for HLA Class I Molecules That Modulate Function of Lymphoid and Myeloid Cells

Abstract

Immunoglobulin-like transcripts (ILTs) encode several Ig-SF receptors which are structurally and functionally related to killer cell inhibitory receptors (KIRs) and are expressed on lymphoid and/or on myeloid cells (Yokoyama 1997 Table 1). ILTs are characterized by two or four homologous extracellular Ig-SF domains and can be classified by differing transmembrane and cytoplasmic domains (Samaridis and Colonna 1997). One subset of ILT receptors displays long cytoplasmic tails containing immunoreceptor tyrosine-based inhibitory motifs (ITIMs). These receptors mediate inhibition of cell activation by recruiting protein tyrosine phos-phatase SHP-1 (Cella et al. 1997a; Cosman et al. 1997; Colonna et al. 1997; Arm et al. 1997; Colonna et al. 1998). Another subset of ILT receptors contains short cytoplasmic domains that lack kinase homology or recognizable motifs for signaling mediators. In addition, they are characterized by the presence of a single basic arginine residue within the hydrophobic transmembrane domain (Colonna et al. 1997; Borges et al. 1997). These ILT receptors closely resemble activating natural killer (NK) cell receptors, which share a positively charged lysine residue in the transmembrane domain and a short cytoplasmic domain that lacks sequence motifs implicated in signal transduction (Biassoni et al. 1996). To transduce signals, activating NK cell receptors associate with an immunoreceptor tyrosine-based activation motif (ITAM)-containing subunit called DAP 12 (Olcese et al. 1997; Lanier et al. 1998a, b; Smith et al. 1998; Campbell et al. 1998). Because of these structural similarities, it seems most likely that ILT receptors with short cytoplasmic tails also activate cells and use an associated protein to transduce stimulatory signals.