Table 1.
Expression, ligands, signaling properties, and function of selected ITEM-containing receptors (ITIM-R)
| Ligands
|
Selected Examples
|
|||||
|---|---|---|---|---|---|---|
| Receptor | Expression | Extracellular | Intracellular | SHP substrate | Inhibition (activation)* of: | Refs |
| FcγRIIb | B, mast, myeloid | Multivalent IgG | SHIP, SHP† | Sustained Ca2+ flux, FcR signaling | (108, 109) | |
| KIR‡ (human) (CD158) | NK,T§ | MHC class I (MHC-I) | SHP | Vavl | Early Ca2+ flux, Tyr-phosphorylation, cytotoxicity, cytokine secretion
β2 integrin-mediated adhesion |
(28,47,110)
(111) (112) (51) |
| Ly49‡ (mouse) | NK,T | MHC-I | SHP | NK cell activation | (7, 18) | |
| CD94/NKG2A‡ | NK,T | HLA-E (human), Qal (mouse) | SHP | NK cell activation
Lysis of CD4+ activated T cells |
(113,114)
(98) |
|
| NKR-P1 (CD161) | NK,T | LLT1 (human) Ocil/Clrb (mouse) | SHP | NK cell activation | (115,116)
(44,117,118) |
|
| LILR‡ (human) (ILT, LIR, CD85) | Broad | MHC-I | SHP, Csk | NK and T cell activation, T cell stimulation by DC | (42,119)
(120) |
|
| PIRB‡ (mouse) | Broad, including brain | MHC-I | SHP | BCR and FcεRI signaling, DC maturation, integrin signaling, GvHD, neuronal plasticity | (62, 121)
(122) (63,64) |
|
| Kirl2 (mouse) | Regions of neuro-genesis in brain | (123) | ||||
| SIRPα‡ (CD172a) | Myeloid | CD47, SP-A/D | SHP, Csk, Pyk2, Grb2, etc. | Cell growth, phagocytosis, adhesion | (65, 124–126) | |
| PD-1 | T | PD-1L | SHP | Autoimmunity, anti-viral
CDS T cell responses |
(56)
(58) |
|
| BTLA | B, T | SHP | Autoimmunity, proliferation | (60,61) | ||
| CD22 (Siglec-2) | B | Sialic acids | SHP, Grb2, SLP76 | SLP-76 | BCR basal signals, (Ca2+ efflux) | (66, 76, 127)
(67) |
| Siglecs‡ (CD33 and CD33-related) | Broad | Sialic acids | SHP, SOCS3 | Proliferation, adhesion | (128, 129) | |
| CD72 | B | CDS | SHP, Grb2 | CD72 | Complex regulation of BCR signaling | (73) |
| LAIR-1 | Broad | Collagen | SHP, Csk | (77, 130) | ||
| KLRG1 | NK, T, mast | Cadherins | SHP, SHIP | NK cell anti-viral response, TCR signaling | (131-134) | |
| gp49B (mouse) | Mast, NK, T neutrophils, eosinophils | αvβ3 integrin | SHP | Allergy, T cell activation, intravascular neutrophil adhesion, eosinophilia | (135, 136)
(137) (138) |
|
| PECAM-1 (CD31) | Platelets, T, endothelium, others | PECAM-1 | SHP | TCR signaling, (NK cell transmigration, endothelial cell motility, integrin-mediated adhesion) | (139-142)
(143) (144) (145) |
|
| CEACAM-1 (CD66a) | Broad | CEACAM-1/5/6/8, CD62E, galectin-3 | SHP | NK and T cell activation, tumor cell growth | (146, 147)
(148) |
|
| TLT-1 | Myeloid, platelets | SHP | (Ca2+ flux) | (149) | ||
| CD300a/f (IRp60, IREM-1/2) | Myeloid, NK | SHP, PI3K | NK cell activation, eosinophil activation | (150-152) | ||
| CLM-1 (mouse) (CMRF-35-like) | Myeloid | SHP | Osteoclastogenesis | (153) | ||
| PILRᇠ| Myeloid | CD99 | SHP | (154, 155) | ||
*
Activating signals of ITIM-Rs are given in parentheses.
†
Includes SHP-1 and SHP-2. Preferential association with SHP-1 or SHP-2 occurs with some ITIMs.
‡
Receptor family, which includes activating and inhibitory receptors.
§
Some T cells, primarily those in the memory subset and IL-15-activated intra-epithelial lymphocytes, express NK cell receptors.