CD278
From Wikipedia, the free encyclopedia
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Inducible T-cell co-stimulator
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| Identifiers | |||||||||||
| Symbol(s) | ICOS; AILIM; CD278; MGC39850 | ||||||||||
| External IDs | OMIM: 604558 MGI: 1858745 HomoloGene: 8097 | ||||||||||
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| RNA expression pattern | |||||||||||
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| Orthologs | |||||||||||
| Human | Mouse | ||||||||||
| Entrez | 29851 | 54167 | |||||||||
| Ensembl | ENSG00000163600 | ENSMUSG00000026009 | |||||||||
| Uniprot | Q9Y6W8 | Q3V3X2 | |||||||||
| Refseq | NM_012092 (mRNA) NP_036224 (protein) |
NM_017480 (mRNA) NP_059508 (protein) |
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| Location | Chr 2: 204.51 - 204.53 Mb | Chr 1: 60.92 - 60.94 Mb | |||||||||
| Pubmed search | [1] | [2] | |||||||||
Inducible T-cell co-stimulator, also known as ICOS, is a human gene.[1]
CD278 or ICOS (Inducible T-cell COStimulator) is a CD28-superfamily costimulatory molecule that is expressed on activated T cells. It is thought to be important for Th2 cells in particular.[2][3]
The protein encoded by this gene belongs to the CD28 and CTLA-4 cell-surface receptor family. It forms homodimers and plays an important role in cell-cell signaling, immune responses, and regulation of cell proliferation.[1]
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[edit] ICOS knockout phenotype
Compared to wild-type naïve T cells, ICOS-/- T cells activated with plate-bound anti-CD3 have reduced proliferation and IL-2 secretion(1). The defect in proliferation can be rescued by addition of IL-2 to the culture, suggesting the proliferative defect is due to reduced IL-2 secretion. In terms of Th1 and Th2 cytokine secretion, ICOS-/- CD4+ T cell activated in vitro have reduced IL-4 secretion, but similar IFN-g secretion. Similarly, CD4+ T cells purified from ICOS-/- mice immunized with the protein keyhole limpet hemocyanin (KLH) in alum or Complete Freunds Adjuvant have attenuated IL-4 secretion, but similar IFN-g and IL-5 secretion when recalled with KLH. These data are similar to an airway hypersensitivity model showing similar IL-5 secretion, but reduced IL-4 secretion in response to sensitization with Ova protein, indicating a defect in Th2 cytokine secretion, but not a defect in Th2 differentiation as both IL-4 and IL-5 are Th2-associated cytokines. In agreement with reduced Th2 responses, ICOS-/- mice have reduced germinal center formation and IgG1 and IgE antibody titers in response to immunization.
[edit] References
- ^ a b Entrez Gene: ICOS inducible T-cell co-stimulator.
- ^ Rudd CE, Schneider H (2003). "Unifying concepts in CD28, ICOS and CTLA4 co-receptor signalling". Nat. Rev. Immunol. 3 (7): 544–56. doi:. PMID 12876557.
- ^ Dong C, Juedes AE, Temann UA, Shresta S, Allison JP, Ruddle NH, Flavell RA (2001). "ICOS co-stimulatory receptor is essential for T-cell activation and function". Nature 409 (6816): 97–101. doi:. PMID 11343121.
[edit] Further reading
- Flesch IE (2003). "Inducible costimulator (ICOS).". J. Biol. Regul. Homeost. Agents 16 (3): 214–6. PMID 12456021.
- Shilling RA, Bandukwala HS, Sperling AI (2006). "Regulation of T:B cell interactions by the inducible costimulator molecule: does ICOS "induce" disease?". Clin. Immunol. 121 (1): 13–8. doi:. PMID 16790364.
- Hutloff A, Dittrich AM, Beier KC, et al. (1999). "ICOS is an inducible T-cell co-stimulator structurally and functionally related to CD28.". Nature 397 (6716): 263–6. doi:. PMID 9930702.
- Yoshinaga SK, Whoriskey JS, Khare SD, et al. (2000). "T-cell co-stimulation through B7RP-1 and ICOS.". Nature 402 (6763): 827–32. doi:. PMID 10617205.
- Ling V, Wu PW, Finnerty HF, et al. (2000). "Cutting edge: identification of GL50, a novel B7-like protein that functionally binds to ICOS receptor.". J. Immunol. 164 (4): 1653–7. PMID 10657606.
- Aicher A, Hayden-Ledbetter M, Brady WA, et al. (2000). "Characterization of human inducible costimulator ligand expression and function.". J. Immunol. 164 (9): 4689–96. PMID 10779774.
- Machado RD, Pauciulo MW, Fretwell N, et al. (2001). "A physical and transcript map based upon refinement of the critical interval for PPH1, a gene for familial primary pulmonary hypertension. The International PPH Consortium.". Genomics 68 (2): 220–8. doi:. PMID 10964520.
- Tezuka K, Tsuji T, Hirano D, et al. (2000). "Identification and characterization of rat AILIM/ICOS, a novel T-cell costimulatory molecule, related to the CD28/CTLA4 family.". Biochem. Biophys. Res. Commun. 276 (1): 335–45. doi:. PMID 11006126.
- Wang S, Zhu G, Chapoval AI, et al. (2000). "Costimulation of T cells by B7-H2, a B7-like molecule that binds ICOS.". Blood 96 (8): 2808–13. PMID 11023515.
- Breitfeld D, Ohl L, Kremmer E, et al. (2001). "Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production.". J. Exp. Med. 192 (11): 1545–52. PMID 11104797.
- Beier KC, Hutloff A, Dittrich AM, et al. (2001). "Induction, binding specificity and function of human ICOS.". Eur. J. Immunol. 30 (12): 3707–17. PMID 11169414.
- Ling V, Wu PW, Finnerty HF, et al. (2002). "Assembly and annotation of human chromosome 2q33 sequence containing the CD28, CTLA4, and ICOS gene cluster: analysis by computational, comparative, and microarray approaches.". Genomics 78 (3): 155–68. doi:. PMID 11735222.
- Lee YH, Ji JD, Sohn J, Song GG (2002). "Polymorphsims of CTLA-4 exon 1 +49, CTLA-4 promoter -318 and Fas promoter -670 in spondyloarthropathies.". Clin. Rheumatol. 20 (6): 420–2. PMID 11771526.
- Haimila KE, Partanen JA, Holopainen PM (2002). "Genetic polymorphism of the human ICOS gene.". Immunogenetics 53 (12): 1028–32. doi:. PMID 11904679.
- Wang S, Zhu G, Tamada K, et al. (2002). "Ligand binding sites of inducible costimulator and high avidity mutants with improved function.". J. Exp. Med. 195 (8): 1033–41. PMID 11956294.
- Riley JL, Mao M, Kobayashi S, et al. (2002). "Modulation of TCR-induced transcriptional profiles by ligation of CD28, ICOS, and CTLA-4 receptors.". Proc. Natl. Acad. Sci. U.S.A. 99 (18): 11790–5. doi:. PMID 12195015.
- Witsch EJ, Peiser M, Hutloff A, et al. (2002). "ICOS and CD28 reversely regulate IL-10 on re-activation of human effector T cells with mature dendritic cells.". Eur. J. Immunol. 32 (9): 2680–6. doi:. PMID 12207353.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:. PMID 12477932.
- Grimbacher B, Hutloff A, Schlesier M, et al. (2003). "Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency.". Nat. Immunol. 4 (3): 261–8. doi:. PMID 12577056.
[edit] External links
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This article incorporates text from the United States National Library of Medicine, which is in the public domain.
[edit] References
11111 C. Dong, A. E. Juedes, U. A. Temann et al., Nature 409 (6816), 97 (2001).
