CD4: Diferenzas entre revisións

En [[bioloxía molecular]], o '''CD4''' ([[cluster de diferenciación|''cluster'' de diferenciación]] 4) é unha [[glicoproteína]] que se encontra na superficie de células inmunes como o [[linfocito T axudante]], [[monocito]], [[macrófago]], e [[célula dendrítica]]. Descubriuse a finais da década de 1970 e orixinalmente deuselle o nome de leu-3 e T4 (debido aos [[anticorpo monoclonal|anticorpos monoclonais]] OKT4 que reaccionaban con el) antes de ser rebautizado como CD4 en 1984.<ref name="isbn0-387-12056-4">{{Cita libro | author = Alain Bernard | authorlink = | editor = | others = | title = Leucocyte typing: human leucocyte differentiation antigens detected by monoclonal antibodies: specification, classification, nomenclature: [report on the first international references workshop sponsored by INSERM, WHO and IUIS] | edition = | language = | publisher = Springer | location = Berlin | year = 1984 | origyear = | pages = pages 45–48 | quote = | isbn = 0-387-12056-4 | oclc = | doi = | url = | accessdate =}}</ref> Nos humanos a proteína CD4 está codificada polo [[xene]] ''CD4'' do [[cromosoma 12]].<ref name="pmid3086883">{{citeCita journalpublicación periódica | author = Isobe M, Huebner K, Maddon PJ, Littman DR, Axel R, Croce CM | title = The gene encoding the T-cell surface protein T4 is located on human chromosome 12 | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 83 | issue = 12 | pages = 4399–402 | year = 1986 | month = June | pmid = 3086883 | pmc = 323740 | doi = 10.1073/pnas.83.12.4399| url = http://www.pnas.org/cgi/pmidlookup?view=long&pmid=3086883 }}</ref><ref name="pmid8723724">{{citeCita journalpublicación periódica | author = Ansari-Lari MA, Muzny DM, Lu J, Lu F, Lilley CE, Spanos S, Malley T, Gibbs RA | title = A gene-rich cluster between the CD4 and triosephosphate isomerase genes at human chromosome 12p13 | journal = Genome Res. | volume = 6 | issue = 4 | pages = 314–26 | year = 1996 | month = April | pmid = 8723724 | doi = 10.1101/gr.6.4.314| url = http://www.genome.org/cgi/pmidlookup?view=long&pmid=8723724 }}</ref>

O CD4 é un [[correceptor]] que axuda ao [[receptor de células T]] (TCR) na súa comunicación coa [[célula presentadora de antíxenos]]. Por medio do seu dominio intraceluar, o CD4 amplifica o sinal xerado polo TCR recrutando o [[encima]] [[tirosina quinase]] [[lck]], que é esencial na activación de moitos compoñentes moleculares da cascada de sinalización dun linfocito T activado. O CD4 tamén interacciona directamente con moléculas do [[MHC de clase II]] na superficie da célula presentadora de antíxenos utilizando o seu dominio extracelular. O dominio extracelular adopta unha estrutura en [[sandwich beta]] de tipo inmunoglobulina con sete cadeas en dúas [[folla beta|follas beta]], formando un [[Folla beta#Motivos estruturais comúns|motivo greca]].<ref name="pmid8493535">{{citeCita journalpublicación periódica | author = Brady RL, Dodson EJ, Dodson GG, Lange G, Davis SJ, Williams AF, Barclay AN | title = Crystal structure of domains 3 and 4 of rat CD4: relation to the NH2-terminal domains | journal = Science | volume = 260 | issue = 5110 | pages = 979–83 | year = 1993 | month = May | pmid = 8493535 | doi = 10.1126/science.8493535| url = }}</ref>

O CD4 tamén interacciona con [[SPG21]],<ref name=pmid11113139>{{citeCita journalpublicación periódica |last=Zeitlmann |first=L |authorlink= |coauthors=Sirim P, Kremmer E, Kolanus W |year=2001|month=Mar. |title=Cloning of ACP33 as a novel intracellular ligand of CD4 |journal=J. Biol. Chem. |volume=276 |issue=12 |pages=9123–32 |publisher= |location = United States| issn = 0021-9258| pmid = 11113139 |doi = 10.1074/jbc.M009270200 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = }}</ref> [[Lck]]<ref name="pmid20724730">{{citeCita journalpublicación periódica | author = Rudd CE, Trevillyan JM, Dasgupta JD, Wong LL, Schlossman SF | title = Pillars article: the CD4 receptor is complexed in detergent lysates to a protein-tyrosine kinase (pp58) from human T lymphocytes. 1988 | journal = J. Immunol. | volume = 185 | issue = 5 | pages = 2645–9 | year = 2010 | month = September | pmid = 20724730 | doi = | url = }}</ref><ref name="pmid2455897">{{citeCita journalpublicación periódica | author = Rudd CE, Trevillyan JM, Dasgupta JD, Wong LL, Schlossman SF | title = The CD4 receptor is complexed in detergent lysates to a protein-tyrosine kinase (pp58) from human T lymphocytes | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 85 | issue = 14 | pages = 5190–4 | year = 1988 | month = July | pmid = 2455897 | pmc = 281714 | doi = 10.1073/pnas.85.14.5190| url = }}</ref><ref name="pmid2470098">{{citeCita journalpublicación periódica | author = Barber EK, Dasgupta JD, Schlossman SF, Trevillyan JM, Rudd CE | title = The CD4 and CD8 antigens are coupled to a protein-tyrosine kinase (p56lck) that phosphorylates the CD3 complex | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 86 | issue = 9 | pages = 3277–81 | year = 1989 | month = May | pmid = 2470098 | pmc = 287114 | doi = 10.1073/pnas.86.9.3277| url = }}</ref><ref name="pmid12007789">{{citeCita journalpublicación periódica | author = Hawash IY, Hu XE, Adal A, Cassady JM, Geahlen RL, Harrison ML | title = The oxygen-substituted palmitic acid analogue, 13-oxypalmitic acid, inhibits Lck localization to lipid rafts and T cell signaling | journal = Biochim. Biophys. Acta | volume = 1589 | issue = 2 | pages = 140–50 | year = 2002 | month = April | pmid = 12007789 | doi = 10.1016/S0167-4889(02)00165-9 }}</ref><ref name="pmid11854499">{{citeCita journalpublicación periódica | author = Foti M, Phelouzat MA, Holm A, Rasmusson BJ, Carpentier JL | title = p56Lck anchors CD4 to distinct microdomains on microvilli | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 99 | issue = 4 | pages = 2008–13 | year = 2002 | month = February | pmid = 11854499 | pmc = 122310 | doi = 10.1073/pnas.042689099 | url = }}</ref> e co [[homólogo da proteína unc-119]].<ref name="pmid14757743">{{citeCita journalpublicación periódica | author = Gorska MM, Stafford SJ, Cen O, Sur S, Alam R | title = Unc119, a Novel Activator of Lck/Fyn, Is Essential for T Cell Activation | journal = J. Exp. Med. | volume = 199 | issue = 3 | pages = 369–79 | year = 2004 | month = February | pmid = 14757743 | pmc = 2211793 | doi = 10.1084/jem.20030589 }}</ref>

O [[VIH-1]] utiliza o CD4 para introducirse dentro das células T [[hospede]]s ao unirse a el pola proteína [[gp120]] da [[envoltura viral]].<ref name="pmid9641677">{{citeCita journalpublicación periódica | author = Kwong PD, Wyatt R, Robinson J, Sweet RW, Sodroski J, Hendrickson WA | title = Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody | journal = Nature | volume = 393 | issue = 6686 | pages = 648–59 | year = 1998 | month = June | pmid = 9641677 | doi = 10.1038/31405 }}</ref> A unión ao CD4 crea un cambio na conformación da gp120 que lle permite ao VIH-1 unirse ao correceptor expresado na célula hóspede chamado [[receptor de quimocina]] [[CCR5]] ou [[CXCR4]]. Despois dun cambio estrutural noutra proteína viral (a [[gp41]]), o [[VIH]] insire un [[péptido de fusión]] na célula hóspede que fai que a membrana externa do virus se fusione coa [[membrana plasmática]] celular.

A infección por VIH produce unha progresiva redución do número de [[célula T axudante|células T axudantes CD4+]]. O reconto de CD4 utilízase para decidir cando se empeza o tratamento durante a infección por VIH e posteriormente para avaliar a eficacia do tratamento. Os valores sanguíneos normais exprésanse xeralmente como o número de células por microlitro (ou milímetro cúbico, mm³) de sangue, con valores normais para as células CD4 de entre 500 e 1200 células/mm³.<ref name="pmid1349272">{{citeCita journalpublicación periódica | author = Bofill M, Janossy G, Lee CA, MacDonald-Burns D, Phillips AN, Sabin C, Timms A, Johnson MA, Kernoff PB | title = Laboratory control values for CD4 and CD8 T lymphocytes. Implications for HIV-1 diagnosis | journal = Clin. Exp. Immunol. | volume = 88 | issue = 2 | pages = 243–52 | year = 1992 | month = May | pmid = 1349272 | pmc = 1554313 | doi = | url = }}</ref> Un reconto de CD4 mide o número de células T que expresan o CD4, e serve para avaliar o estado do sistema inmunitario do paciente, aínda que non mide directamente a cantidade de virus (por exemplo, a presenza de ADN viral, ou de [[anticorpo]]s específicos contra o virus). Xeralmente o tratamento comeza cando os recontos de CD4 chegan a 350 células por microlitro (con valores de menos de 200 considérase que o individuo infectado ten [[SIDA]]).

O CD4 continúa expresándose na maioría dos [[neoplasma]]s derivados de células T axudantes. É por tanto posible utilizar a [[inmunohistoquímica]] do CD4 en mostras de [[biopsia]]s de tecidos para identificar a maioría das formas de [[linfoma]]s de células T periféricas e condicións malignas asociadas.<ref name="isbn1-84110-100-1">{{Cita libro | author = Kumarasen Cooper; Anthony S-Y. Leong | title = Manual of diagnostic antibodies for immunohistology | publisher = Greenwich Medical Media | location = London | year = 2003 | pages = 65 | isbn = 1-84110-100-1}}</ref> Este antíxeno foi tamén asociado con varias [[enfermidade autoinmunitaria|enfermidades autoinmunitarias]] como a [[vitilixe]] e a [[diabetes mellitus tipo I]].<ref name="pmid19843086">{{citeCita journalpublicación periódica | author = Zamani M, Tabatabaiefar MA, Mosayyebi S, Mashaghi A, Mansouri P | title = Possible association of the CD4 gene polymorphism with vitiligo in an Iranian population | journal = Clin. Exp. Dermatol. | volume = 35 | issue = 5 | pages = 521–4 | year = 2010 | month = July | pmid = 19843086 | doi = 10.1111/j.1365-2230.2009.03667.x }}</ref>

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