Receptor (Ligand) Intracellular motif Mechanism of Action Receptor distribution Ligand distribution Disease Biologic (Target) Refs.
CTLA-4 (CD80, CD86) YxxM 1Use of intracellular mediators–SHP-2, PI3K
3
Ectodomain competition–with counter receptor (CD28); interference of lipid-raft and microcluster formation
Activated T cells B cells, Mo, DCs, T cells, inducible in some somatic tissues RA, MS, LN, Melanoma abatacept (B7)             ipilimumab (CTLA-4)   tremelimumab (CTLA-4) [31,89] [13,90] [34,91]
PD-1 (PD-L1, PD-L2) ITIM, ITSM 1Use of intracellular mediators– recruitment of SHP-1, SHP-2; suppression of transcription factor SKP2
2Inducing genes that negatively regulate T cell signalling– BATF
Activated T cells, B cells, DCs, NKT cells, Mo B cells, T cells, inducible in Mo, DCs, some somatic tissues Melanoma, RCC, HIV CT-011(PD-1)    MDX1106 (PD-1)   MPDL3280A (PD-L1) [41,92] [93,94] [95]
BTLA (HVEM) ITIM, ITSM 1Use of intracellular mediators–SHP-1, SHP-2
3Ectodomain competition with counter receptor (LIGHT)
T cells, B cells, DCs,  Myeloid cells naive T cells, B cells, DCs, NK cells, myeloid cells, inducible in somatic tissues GVHD, Autoimmune diabetes N/A [51,52]
LAG-3 (MHC II) KIEELE 3Ectodomain competition with counter receptor (CD4) T cells, B cells, NK cells DCs, MΦ, B cells, Mo, thymic epithelial cells Melanoma, RCC IMP321 (MHC II) [96,97] [58]
TIM-3 (Galectin-9, PS) Y235, Y242 1Use of intracellular mediators–Lck, Fyn, p85 PI3K,  Bat3 (repressor of TIM-3 signalling) T cells, B cells, NK cells, NKT cells, DCs, MΦ T cells, eosinophils, endothelial cells, DCs, MΦ MS, colitis, HIV, HCV N/A [66,69] [64,70]
LAIR-1 (Collagen) 2×ITIM 1Use of intracellular mediators–SHP-1, SHP-2, Csk T cells, B cells, NK cells, DCs, Mo, eosinophils, Basophils, Mast cells Extracellular matrix components RA N/A [71]
TIGIT (CD155) 2×ITIM 3Ectodomain competition with the counter receptor (CD266) T cells, NK cells T cells, B cells, DCs MS N/A [77,78]
Siglecs (sialylated glycoconjugates) variable number of ITIM, Grb2 and ITIM-like domains 1Use of intracellular mediators–SHP-1, SHP-2, PI3K
3Ectodomain competition with the counter receptor (cis/trans-ligand binding)
T cells, B cells, DCs, pDCs, MΦ, Mo, Neutrophils, NK cells, eosinophils widespread on cell surfaces, proteins, pathogens Leukaemia, SLE, B cell-NHL gemtuzumab (Siglec-3), epratuzumab (Siglec-2) [98,99]
Abbreviations: 1-3 three general types of distinct mechanisms of action; B cell-NHL: B cell non Hodgkin’s Lymphomas; Bat3- Human Leukocyte Antigen B (HLA-B)-associated Transcript 3; BATF: Basic Leucine Zipper Transcription Factor, ATF-like; BTLA: B- and T-lymphocyte Attenuator; Csk: COOH-terminal; CTLA-4: Cytotoxic T-Lymphocyte Antigen 4; DC: Dendritic Cells; Fyn: a Src family tyrosine-protein kinase; Grb2: Growth factor receptor-bound protein 2; GVDH: Graft Versus Host Disease; HCV: Hepatitis C Virus; HIV: Human Immunodeficiency Virus; HVEM: Herpes Virus Entry Mediator; ITIM- Immunoreceptor Tyrosine-based Inhibition Motif; ITSM: Immunoreceptor Tyrosinebased Switch Motif; LAG-3: Lymphocyte-Activation Gene 3; LAIR-1: Leukocyte-Associated Immunoglobulin-like Receptor 1; Lck: Lymphocyte-specific protein tyrosine kinase; LIGHT: Lymphotoxin-like, exhibits inducible expression, and competes with herpes simplex virus glycoprotein D for HVEM, a receptor expressed by T lymphocytes; LN: Lupus Nephritis; MHC II: Major Histocompatibility Complex II; Mo: Monocyte; MS: Multiple Sclerosis; MΦ: Macrophage; N/A: Not Applicable; NK: Natural Killer cells; NKT: Natural Killer T cells; PD-1: Programmed cell death protein 1; pDC: plasmacytoid dendritic cell; PD-L1: Programmed cell death 1 ligand 1; PI3K: Phosphoinositide 3-kinase; PS: Phosphatidyl Serine; RA: Rheumatoid Arthritis; RCC: Renal Cell Carcinoma; SHP-1/2/: Src homology 2-containing tyrosine phosphatase 1/2/; Siglecs: Sialic acid binding Ig-like lectins; SLE: Systemic Lupus erythematous, Srk kinase; SKP2: S-phase Kinase-associated Protein 2; TIGIT: T-cell immunoreceptor with immunoglobulin and ITIM domains; TIM-3: T cell Immunoglobulin Mucin-3
Table 1: T cell co-inhibitory receptors.