This MedLibrary.org supplementary page on CTLA-4 is provided directly from the open source Wikipedia as a service to our readers. Please see the note below on authorship of this content, as well as the Wikipedia usage guidelines. To search for other content from our encyclopedia supplement, please use the form below:
Related Sponsors
 |
The introduction to this April 2007 provides insufficient context for those unfamiliar with the subject. Please help improve the article with a good introductory style. |
|
Cytotoxic T-lymphocyte-associated protein 4
|
|||||||||||
 |
|||||||||||
| Structure of murine CTLA4 (CD152) | |||||||||||
| Available structures: 1ah1, 1i85, 1i8l | |||||||||||
| Identifiers | |||||||||||
| Symbols | CTLA4; CD152; CELIAC3; CTLA-4; GSE; IDDM12 | ||||||||||
| External IDs | OMIM: 123890 MGI: 88556 HomoloGene: 3820 | ||||||||||
|
|||||||||||
| RNA expression pattern | |||||||||||
|
|
|||||||||||
| Orthologs | |||||||||||
| Human | Mouse | ||||||||||
| Entrez | 1493 | 12477 | |||||||||
| Ensembl | ENSG00000163599 | ENSMUSG00000026011 | |||||||||
| Uniprot | P16410 | Q6GTR6 | |||||||||
| Refseq | XM_001129541 (mRNA) XP_001129541 (protein) |
NM_009843 (mRNA) NP_033973 (protein) |
|||||||||
| Location | Chr 2: 204.44 - 204.45 Mb | Chr 1: 60.85 - 60.86 Mb | |||||||||
| Pubmed search | [1] | [2] | |||||||||
CTLA4 (Cytotoxic T-Lymphocyte Antigen 4) is a CD28-family receptor expressed on mainly CD4+ T cells. It binds the same ligands as CD28 (CD80 and CD86 on B cells and dendritic cells), but with higher affinity than CD28. However, in contrast to CD28 which enhances cell function when bound at the same time as the T cell receptor, CTLA4 inhbits the T cell and prevents it from functioning.1 Intracellular CTLA4 is also found in regulatory T cells and may be important to their function. T cell activation through the T cell receptor and CD28 leads to increased expression of CTLA-4, an inhibitory receptor for B7 molecules (i.e. CD80 and CD 86).
The intracellular domain is similar to that of CD28, in that it has no intrinsic catalytic activity and contains one YVKM motif able to bind PI3K, PP2A and SHP-2 and one proline-rich motif able to bind SH3 containing proteins. The first role of CTLA-4 in inhibiting T cell responses seem to be directly via SHP-2 and PP2A dephosphorylation of TCR-proximal signalling proteins such as CD3 and LAT. CTLA-4 can also affect signalling indirectly via competing with CD28 for CD80/86 binding. CTLA-4 can also bind PI3K, although the importance and results of this interaction are uncertain.
Clinical significance
The comparatively higher binding affinity of CTLA4 has made it a potential therapy for autoimmune diseases. It plays a role in the initial immune response to and infection of immune cells by HIV, along with the CD-1 pathway and others. Fusion proteins of CTLA4 and antibodies (CTLA4-Ig) have been used in clinical trials for rheumatoid arthritis.2 The fusion protein CTLA4-Ig is commercially available as Orencia (abatacept). A second generation form of CTLA4-Ig known as belatacept is currently being tested in trials. Both of these compounds are expected to find wide use in organ transplantation.
Polymorphisms of the CTLA-4 gene are associated with autoimmune diseases such as autoimmune thyroid disease and multiple sclerosis, though this association is often weak. In Systemic Lupus Erythematosus (SLE), the splice variant sCTLA-4 is found to be aberrantly produced and found in the serum of patients with active SLE.
References
- ^ Waterhouse P, Penninger JM, Timms E et al.. "Lymphoproliferative disorders with early lethality in mice deficient in CTLA-4". Science 270 (985). PMID 7481803.
- ^ Arthritis Research & Therapy | Meeting Abstract | Abatacept (CTLA4Ig) treatment increases the remission rate in rheumatoid arthritis patients refractory to methotrexate treatment
Further reading
- Liossis SN, Sfikakis PP, Tsokos GC (1998). "Immune cell signaling aberrations in human lupus.". Immunol. Res. 18 (1): 27–39. PMID 9724847.
- Chang TT, Kuchroo VK, Sharpe AH (2002). "Role of the B7-CD28/CTLA-4 pathway in autoimmune disease.". Curr. Dir. Autoimmun. 5: 113–30. PMID 11826754.
- Alizadeh M, Babron MC, Birebent B, et al. (2003). "Genetic interaction of CTLA-4 with HLA-DR15 in multiple sclerosis patients.". Ann. Neurol. 54 (1): 119–22. doi:. PMID 12838528.
- Chistiakov DA, Turakulov RI (2004). "CTLA-4 and its role in autoimmune thyroid disease.". J. Mol. Endocrinol. 31 (1): 21–36. PMID 12914522.
- Vaidya B, Pearce S (2004). "The emerging role of the CTLA-4 gene in autoimmune endocrinopathies.". Eur. J. Endocrinol. 150 (5): 619–26. PMID 15132716.
- Brand O, Gough S, Heward J (2007). "HLA , CTLA-4 and PTPN22 : the shared genetic master-key to autoimmunity?". Expert reviews in molecular medicine 7 (23): 1–15. doi:. PMID 16229750.
- Kavvoura FK, Akamizu T, Awata T, et al. (2007). "Cytotoxic T-lymphocyte associated antigen 4 gene polymorphisms and autoimmune thyroid disease: a meta-analysis.". J. Clin. Endocrinol. Metab. 92 (8): 3162–70. doi:. PMID 17504905.
Wikipedia content modification information:
- This page was last modified on 16 July 2008, at 01:52.
Wikipedia Authorship and Review
Wikipedia content provided here is not reviewed directly by MedLibrary.org. Wikipedia content is authored by an open community of volunteers and is not produced by or in any way affiliated with MedLibrary.org.
Wikipedia Usage Guidelines
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article on "CTLA-4".
The URL for this specific entry is:
All Wikipedia text is available under the terms of the GNU Free Documentation License. (See Copyrights for details). Wikipedia® is a registered trademark of the Wikimedia Foundation, Inc.