Other immune checkpoint proteins

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Immune checkpoint proteins
Other immune checkpoint proteins

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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Checkpoint proteins include co-inhibitory and co-stimulatory receptors on immune effectors cells. Blocking monoclonal antibodies (mAbs) to co-inhibitory receptors such as PD-1 and CTLA4 have sucessfully entered clinical practice as cancer immunotherapies. Co-stimulatory receptors such as GITR, ICOS and OX40 are being targeted by immunostimulatory mAbs in preclinical and clinical development programmes [3,14].

Targets

Targets of relevance to immunopharmacology are highlighted in blue

SIGLEC2 (CD22) Show summary »« Hide summary More detailed page go icon to follow link

Target Id	2786
Nomenclature	CD22
Common abbreviation	SIGLEC2
Previous and unofficial names	B-lymphocyte cell adhesion molecule \| sialic acid binding Ig-like lectin 2 \| SIGLEC-2
Genes	CD22 (Hs)
Ensembl ID	ENSG00000012124 (Hs)
UniProtKB AC	P20273 (Hs)

CD28 Show summary »« Hide summary More detailed page go icon to follow link

Target Id

2863

Nomenclature

CD28

Previous and unofficial names

cluster of differentiation 28 | CD28 antigen (Tp44)

Genes

CD28 (Hs), Cd28 (Mm), Cd28 (Rn)

Ensembl ID

ENSG00000178562 (Hs), ENSMUSG00000026012 (Mm), ENSRNOG00000010283 (Rn)

UniProtKB AC

P10747 (Hs), P31041 (Mm), P31042 (Rn)

Antibodies

lulizumab pegol (Binding) pK_d 9.3 – 9.4 [15]

Comment

CD28 is expressed on the surface of T cells and is required for the co-stimulatory signal essential for the activation and survival of T cells. CD28 acts in concert with the T cell receptor to stimulate cytokine release. The B7 proteins CD80 and CD86 on the surface of antigen presenting cells bind CD28.
As a drug target, CD28 modulation is being investigated as a treatment for autoimmume conditions.

SIGLEC3 (CD33) C Show summary »« Hide summary More detailed page go icon to follow link

CD80 C Show summary »« Hide summary More detailed page go icon to follow link

LILRB1 (leukocyte immunoglobulin like receptor B1 (CD85j)) Show summary »« Hide summary More detailed page go icon to follow link

Target Id	2973
Nomenclature	leukocyte immunoglobulin like receptor B1 (CD85j)
Common abbreviation	LILRB1
Previous and unofficial names	ILT2 \| leucocyte Ig-like receptor B1 \| leukocyte immunoglobulin-like receptor, subfamily B (with TM and ITIM domains), member 1 \| LIR-1 \| LIR1 \| MIR-7 \| myeloid inhibitory receptor 7 \| PIR-B \| PIRB
Genes	LILRB1 (Hs)
Ensembl ID	ENSG00000104972 (Hs)
UniProtKB AC	Q8NHL6 (Hs)

CD86 C Show summary »« Hide summary More detailed page go icon to follow link

CTLA-4 (cytotoxic T-lymphocyte-associated protein 4 (CD152)) C Show summary »« Hide summary More detailed page go icon to follow link

Target Id

2743

Nomenclature

cytotoxic T-lymphocyte-associated protein 4 (CD152)

Common abbreviation

CTLA-4

Previous and unofficial names

ICOS | cytotoxic T-lymphocyte-associated protein 4

Genes

CTLA4 (Hs), Ctla4 (Mm), Ctla4 (Rn)

Ensembl ID

ENSG00000163599 (Hs), ENSMUSG00000026011 (Mm), ENSRNOG00000054129 (Rn)

UniProtKB AC

P16410 (Hs), P09793 (Mm)

Antibodies

ipilimumab (Binding) pK_d >9.0 [6]

tremelimumab (Binding) pK_d 8.9 [8]

LAG3 (CD223) / CD223 Show summary »« Hide summary More detailed page go icon to follow link

Target Id	2932
Nomenclature	LAG3 (CD223)
Systematic nomenclature	CD223
Genes	LAG3 (Hs), Lag3 (Mm), Lag3 (Rn)
Ensembl ID	ENSG00000089692 (Hs), ENSMUSG00000030124 (Mm), ENSRNOG00000021334 (Rn)
UniProtKB AC	P18627 (Hs), Q61790 (Mm)
Comment	LAG3 is a negative regulator of T cells (a check point immunomodulator) [9]. It is evolutionarily related to CD4 and both proteins share conserved structural motifs, despite only being ~20% homologous at the amino acid level. Divergent biological functions likely reside in their cytoplasmic domains which contain unique structural and molecular differences.

B7-H3 (CD276) Show summary »« Hide summary More detailed page go icon to follow link

ICOS (CD278) Show summary »« Hide summary More detailed page go icon to follow link

Target Id	2939
Nomenclature	ICOS (CD278)
Previous and unofficial names	inducible T-cell costimulator \| activation-inducible lymphocyte immunomediatory molecule \| AILIM \| CVID1 \| inducible costimulator
Genes	ICOS (Hs), Icos (Mm), Icos (Rn)
Ensembl ID	ENSG00000163600 (Hs), ENSMUSG00000026009 (Mm), ENSRNOG00000046196 (Rn)
UniProtKB AC	Q9Y6W8 (Hs), Q9WVS0 (Mm), Q9R1T7 (Rn)

PD-1 (programmed cell death 1 (CD279)) C Show summary »« Hide summary More detailed page go icon to follow link

TIM3 (CD366) Show summary »« Hide summary More detailed page go icon to follow link

ILDR2 (immunoglobulin like domain containing receptor 2) Show summary »« Hide summary More detailed page go icon to follow link

Target Id	2986
Nomenclature	immunoglobulin like domain containing receptor 2
Common abbreviation	ILDR2
Previous and unofficial names	immunoglobulin-like domain containing receptor 2 \| LISCH-like (mouse)
Genes	ILDR2 (Hs), Ildr2 (Mm), Ildr2 (Rn)
Ensembl ID	ENSG00000143195 (Hs), ENSMUSG00000040612 (Mm), ENSRNOG00000025151 (Rn)
UniProtKB AC	Q71H61 (Hs)

PVRIG (PVR related immunoglobulin domain containing) Show summary »« Hide summary More detailed page go icon to follow link

Target Id	3080
Nomenclature	PVR related immunoglobulin domain containing
Common abbreviation	PVRIG
Previous and unofficial names	CD112 receptor \| nectin-2 receptor \| poliovirus receptor related immunoglobulin domain containing \| CD112R
Genes	PVRIG (Hs), Pvrig (Mm), Pvrig (Rn)
Ensembl ID	ENSG00000213413 (Hs), ENSMUSG00000109713 (Mm), ENSRNOG00000051906 (Rn)
UniProtKB AC	Q6DKI7 (Hs)

TIGIT Show summary »« Hide summary More detailed page go icon to follow link

Target Id	2941
Nomenclature	TIGIT
Previous and unofficial names	T-cell immunoreceptor with Ig and ITIM domains \| V-set and immunoglobulin domain containing 9 \| V-set and transmembrane domain containing 3 \| VSIG9 \| VSTM3 \| WUCAM [2]
Genes	TIGIT (Hs), Tigit (Mm), Tigit (Rn)
Ensembl ID	ENSG00000181847 (Hs), ENSMUSG00000071552 (Mm), ENSRNOG00000056574 (Rn)
UniProtKB AC	Q495A1 (Hs), P86176 (Mm)
Comment	TIGIT is an immune checkpoint modulator [9].

VISTA (V-set immunoregulatory receptor) Show summary »« Hide summary More detailed page go icon to follow link

Target Id	2956
Nomenclature	V-set immunoregulatory receptor
Common abbreviation	VISTA
Previous and unofficial names	B7-H5 \| B7H5 \| PD-1H \| programmed death-1 homologue-1 \| V-domain Ig suppressor of T cell activation \| VISTA
Genes	VSIR (Hs), Vsir (Mm), Vsir (Rn)
Ensembl ID	ENSG00000107738 (Hs), ENSMUSG00000020101 (Mm), ENSRNOG00000000569 (Rn)
UniProtKB AC	Q9H7M9 (Hs), Q9D659 (Mm)
Comment	V-set immunoregulatory receptor (VSIR) is commonly referred to as VISTA. It is an Ig superfamily (B7 family) protein that acts as an inhibitory immune-checkpoint molecule.

References

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1. Bernstein ID. (2000) Monoclonal antibodies to the myeloid stem cells: therapeutic implications of CMA-676, a humanized anti-CD33 antibody calicheamicin conjugate. Leukemia, 14 (3): 474-5. [PMID:10720144]

2. Boles KS, Vermi W, Facchetti F, Fuchs A, Wilson TJ, Diacovo TG, Cella M, Colonna M. (2009) A novel molecular interaction for the adhesion of follicular CD4 T cells to follicular DC. Eur J Immunol, 39 (3): 695-703. [PMID:19197944]

3. Cabo M, Offringa R, Zitvogel L, Kroemer G, Muntasell A, Galluzzi L. (2017) Trial Watch: Immunostimulatory monoclonal antibodies for oncological indications. Oncoimmunology, 6 (12): e1371896. [PMID:29209572]

4. Caron PC, Co MS, Bull MK, Avdalovic NM, Queen C, Scheinberg DA. (1992) Biological and immunological features of humanized M195 (anti-CD33) monoclonal antibodies. Cancer Res, 52 (24): 6761-7. [PMID:1458463]

5. Carven GJ, Van Eenennaam H, Dulos GJ. (2010) Antibodies to human programmed death receptor PD-1. Patent number: US20100266617. Assignee: Organon NV. Priority date: 13/06/2008. Publication date: 21/10/2010.

6. Halk EL, Korman AJ, Lonberg N. (2001) Human ctla-4 antibodies and their uses. Patent number: WO2001014424. Assignee: Medarex Inc. Priority date: 24/08/1999. Publication date: 01/03/2001.

7. Hall RD, Gray JE, Chiappori AA. (2013) Beyond the standard of care: a review of novel immunotherapy trials for the treatment of lung cancer. Cancer Control, 20 (1): 22-31. [PMID:23302904]

8. Hanson DC, Neveu MJ, Mueller EE, Hanke JH, Gilman SC, Davis CG, Corvalan JR. (2004) Human monoclonal antibodies to CTLA-4. Patent number: US6682736 B1. Assignee: Abgenix, Inc., Pfizer Inc.. Priority date: 22/12/1998. Publication date: 27/01/2004.

9. Joller N, Anderson AC, Kuchroo VK. (2024) LAG-3, TIM-3, and TIGIT: Distinct functions in immune regulation. Immunity, 57 (2): 206-222. [PMID:38354701]

10. Kline J, Gajewski TF. (2010) Clinical development of mAbs to block the PD1 pathway as an immunotherapy for cancer. Curr Opin Investig Drugs, 11 (12): 1354-9. [PMID:21154117]

11. Korman AJ, Srinivasan M, Wang C, Selby MJ, Chen B, Cardarelli JM. (2006) Human monoclonal antibodies to programmed death 1(pd-1) and methods for treating cancer using anti-pd-1 antibodies alone or in combination with other immunotherapeutics. Patent number: WO2006121168. Assignee: Ono Pharmaceutical Co. Priority date: 09/05/2005. Publication date: 02/03/2015.

12. Latek R, Fleener C, Lamian V, Kulbokas 3rd E, Davis PM, Suchard SJ, Curran M, Vincenti F, Townsend R. (2009) Assessment of belatacept-mediated costimulation blockade through evaluation of CD80/86-receptor saturation. Transplantation, 87 (6): 926-33. [PMID:19300198]

13. Linsley PS, Brady W, Urnes M, Grosmaire LS, Damle NK, Ledbetter JA. (1991) CTLA-4 is a second receptor for the B cell activation antigen B7. J Exp Med, 174 (3): 561-9. [PMID:1714933]

14. Mayes PA, Hance KW, Hoos A. (2018) The promise and challenges of immune agonist antibody development in cancer. Nat Rev Drug Discov, 17 (7): 509-527. [PMID:29904196]

15. Suchard SJ, Davis PM, Kansal S, Stetsko DK, Brosius R, Tamura J, Schneeweis L, Bryson J, Salcedo T, Wang H et al.. (2013) A monovalent anti-human CD28 domain antibody antagonist: preclinical efficacy and safety. J Immunol, 191 (9): 4599-610. [PMID:24081989]

16. Vicente Rabaneda EF, Herrero-Beaumont G, Castañeda S. (2013) Update on the use of abatacept for the treatment of rheumatoid arthritis. Expert Rev Clin Immunol, 9 (7): 599-621. [PMID:23899231]

How to cite this family page

Database page citation:

Other immune checkpoint proteins. Accessed on 19/05/2025. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=949.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Buneman OP, Faccenda E, Harding SD, Spedding M, Cidlowski JA, Fabbro D, Davenport AP, Striessnig J, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Introduction and Other Protein Targets. Br J Pharmacol. 180 Suppl 2:S1-22.