Figure 2. Interactive CHIME of CTLA-4 bind with a B7 molecule. From . (webpage). The green and blue images combined make the CTLA-4 molecule, which is binded to the yellow and pink B7 molecule as a consequence of inhibitory signals to shut down the proliferative phase.
What happens if CTLA-4 is mutated?
I researched information about the mutated CTLA-4 protein but no specific information was obtained to understand what would happen if CTLA-4 was mutated. However, it is possible that if a CTLA-4 molecule is mutated it would not be able to bind to B7 molecules properly, therefore leading to autoimmunity.
Theraputic Applications of CTLA-4
Psoriasis Vulgaris - Psoriasis is a chronic, recurring skin disease. An increase dosage of CTLA-4 for this type of disorder assists in a quantitative decrease in epidermal hyperplasia, which helps bring about quantitative decline in skin-infiltrating T cells (Abrams et al., 1999).
Graves Disease - Graves Disease is an autoimmune disease where the thyroid gland over-produces some of your hormones. Allele sequence of A/G or G/G on nucleotide 49 of the CTLA-4 gene in patients have shown that more people are infected with Graves Disease (Kouki et al., 2000).
Insulin-dependent Diabetes Mellitus - Insulin-dependent Diabetes Mellitus is a medical disorder where there is usually higher blood (sugar) levels after activities. The insulin-dependent diabetes mellitus patients where seen as having a sequence polymorhphism of A\G in the first exon of the CTLA-4 gene (Marron et al., 1997).
Systemic Lupus Erythematosus - Systemic Lupus Erythematosus is a chronic disease which affects joints, muscles and other parts of the body. Barreto et al. (2004) discovered that there is an linkage between the 49A-G SNP in exon 1 of the CTLA-4 gene and Systemic Lupus Erythematosus.
Alegre, Maria-Luisa, Thompson, Craig B., Gajewski, Thomas F; 1998. Second Signals for Lymphocyte Activation: B7 Receptors. Encyclopedia of Immunology. 2nd ed. Vol. 4. San Diego: Academic Press Inc. 2147-2148. Accessed 2006 Mar 13.
Freeman, J. Gordon, Boussiotis, Vassiliki A., Gribben, John G., Sharpe, Arlene H., Nadler Lee M;1998. B7 (CD80 and CD86). Encyclopedia of Immunology. 2nd ed. Vol. 1. San Diego: Academic Press Inc. 306. Accessed 2006 Mar 13.
Alegre, Maria-Luisa, Thompson, Craig B., Gajewski, Thomas F; 1998. Second Signals for Lymphocyte Activation: Cytokine Receptors. Encyclopedia of Immunology. 2nd ed. Vol. 4. San Diego: Academic Press Inc. 2149. Accessed 2006 Mar 13.
Janeway, C., Travers, P. Walport, M., Shlomchik, M. 2001. Immunobiology: The Immune System in Health and Disease. New York, New York: Garland Science Publishing. p. 329. Accessed 2006 Mar 13.
Ostrov, David A., Shi, Wuxian, Schwartz, Jean-Claude D., Almo Steven C., Natheneson, Stanley G. 2000. Structure of Murine CTLA-4 and Its Role in Modulating T Cell Responsiveness. JSTOR: A Journal from the Davidson Library 290 (5492): 816. <http://www.jstor.org/view/00368075/sp030043/03x5169u/0?currentResult=00368075%2bsp030043%2b03x5169u%2b0%2c1F&searchUrl=http%3A%2F%2Fwww.jstor.org%2Fsearch%2FBasicResults%3Fhp%3D25%26si%3D1%26Query%3Dstructure%2Bof%2BCTLA4 >. Accessed 2006 Mar 13.
Abrams, Judith R., Lebwohl, Mark G., Guzzo, Cynthia A., Jegasothy, Brian V., Goldfarb, Michael T., Goffe, Bernard S., Menter, Alan, Lowe, Nicholas J., Krueger, Gerald, Brown, Michael J., Weiner, Russell S., Birkhofer, Martin J., Warner, Garvin L., Berry, Karen K., Linsley, Peter S., Krueger, James G., Ochs, Hans D., Kelley, Susan L., and Kang, Sewon . 1999. CTLA4Ig-mediated blockade of T-cell costimulation in patients with psoriasis vulgaris. < http://www.jci.org/cgi/content/abstract/103/9/1243> Accessed 2006 Mar 15.
Harper, Ling. 1991 and 1999. Cytotoxic T Lymphocyte-Associated 4; CTLA4. < http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=123890> Accessed 2006 Mar 16.
Marron MP., Raffel LJ., Garchon HJ., Jacob CO., Serrano-Rios M., Martinez Larrad MT., Teng WP., Park Y., Zang ZX., Goldstein DR., Tao YW., Beaurain G., Bach JF., Huang HS., Luo DF., Zeidler A., Rotter JI., Yang MC., Modilevsky T., Maclaren NK., She JX. 1997. Insulin-dependent diabetes mellitus (IDDM) is associated with CTLA4 polymorphisms in multiple ethnic groups. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Maclaren+NK%22%5BAuthor%5D> Accessed 2006 Mar 16.
Dariavach. 1988. Cytotoxic T Lymphocyte-Associated 4; CTLA4. < http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=123890> Accessed 2006 Mar 16.
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