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1.
Mucosal Immunol ; 6(2): 235-43, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22763410

RESUMO

Chlamydia trachomatis (Ct) is an obligate intracellular bacterial pathogen. Previously, we showed that infection of human trophoblast cells by Ct triggers the secretion of the pro-inflammatory cytokine, interleukin (IL)-1ß. The aim of this study was to understand the innate immune pathways involved in trophoblast production of IL-1ß after Ct infection. The approach we took was to inhibit the expression or function of the key Toll-like receptors (TLRs), Nod-like receptors, and inflammasome components that have been associated with chlamydia infection. In this study, we report that Ct-induced trophoblast IL-1ß secretion is associated with the transcription of IL-1ß mRNA, the translation and processing of pro-IL-1ß, and the activation of caspase-1. In addition, we demonstrate that Ct-induced IL-1ß production and secretion by the trophoblast is independent of TLR2, TLR4, MyD88, and the Nalp3/ASC inflammasome. Instead we report, for the first time, the importance of Nod1 for mediating trophoblast IL-1ß secretion in response to a Ct infection.


Assuntos
Chlamydia trachomatis/imunologia , Interleucina-1beta/metabolismo , Proteína Adaptadora de Sinalização NOD1/metabolismo , Trofoblastos/metabolismo , Trofoblastos/microbiologia , Proteínas Adaptadoras de Sinalização CARD , Proteínas de Transporte/metabolismo , Linhagem Celular , Proteínas do Citoesqueleto/metabolismo , Expressão Gênica , Humanos , Inflamassomos/metabolismo , Interleucina-1beta/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo
2.
J Immunol ; 165(12): 7285-92, 2000 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-11120863

RESUMO

We recently identified HLA class I-presented epitopes in the major outer membrane protein (MOMP) of Chlamydia trachomatis that elicit CTL responses in human genital tract infections. T cells possessing cytolytic activities specific for these epitopes could be detected following in vitro stimulation of peripheral blood CD8(+) T cells with peptides. In the present study we used HLA-A2 tetramers for detailed characterization of MOMP-specific CTL responses. Ex vivo tetramer analysis detected MOMP-specific T cells in the peripheral blood of infected individuals at significant frequencies (0.01-0.20% of CD8(+) T cells). After in vitro stimulation with peptides, the frequencies of MOMP peptide-specific T cells increased up to 2.34% of CD8(+) T cells in bulk cultures. In contrast, HLA-A2/MOMP tetramer-binding T cells were virtually undetectable in the peripheral blood from uninfected individuals, either ex vivo or after 3 wk of in vitro peptide stimulation of their T cells. Magnetically sorted, tetramer-bound T cells specifically lysed peptide-pulsed targets as well as C. trachomatis-infected epithelial cells with nearly 50-fold greater per cell efficiency than that of unsorted populations. This study provides conclusive evidence of in vivo induction of HLA class I-restricted CD8(+) CTL responses to C. trachomatis MOMP. Direct detection of these cells with tetramers will allow their further characterization without prior manipulation and facilitate monitoring of CTL responses during infections and in immunization trials with MOMP-based vaccines.


Assuntos
Proteínas da Membrana Bacteriana Externa/imunologia , Chlamydia trachomatis/imunologia , Epitopos de Linfócito T/análise , Antígeno HLA-A2/análise , Separação Imunomagnética , Porinas , Linfócitos T Citotóxicos/imunologia , Células Cultivadas , Testes Imunológicos de Citotoxicidade , Epitopos de Linfócito T/imunologia , Epitopos de Linfócito T/metabolismo , Feminino , Antígeno HLA-A2/imunologia , Antígeno HLA-A2/metabolismo , Antígenos HLA-B/análise , Antígenos HLA-B/imunologia , Antígenos HLA-B/metabolismo , Células-Tronco Hematopoéticas/imunologia , Células-Tronco Hematopoéticas/patologia , Humanos , Contagem de Linfócitos , Linfogranuloma Venéreo/imunologia , Masculino , Ligação Proteica/imunologia , Linfócitos T Citotóxicos/metabolismo , Linfócitos T Citotóxicos/patologia
3.
Eur J Immunol ; 30(4): 1203-13, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10760810

RESUMO

Class I molecules, encoded by diverse alleles at several loci of the major histocompatibility complex (MHC) are assembled in the endoplasmic reticulum (ER) from heavy chain, beta2 microglobulin and peptide in association with accessory proteins of the peptide loading complex. We show here, that mutations in the alpha2 domain (Q115A; D122A) of the human class I allele HLA-A2 cause a lack of apparent association with the loading complex and a faster assembly. Despite the drastically reduced association with the TAP loading complex, i. e. less than 20 % of HLA-A2 expressed in the cells can be co-precipitated with either TAP, calreticulin or tapasin, the mutant proteins are expressed on the cell surface in a stable conformation, and bind a complex set of peptides almost identical to that of wild-type HLA-A2. Furthermore, the mutant class I molecules are more rapidly exported from the ER than wild-type HLA-A2 and undergo faster maturation. The mutation Q115A does not destroy a binding site for the loading complex as this HLA-A2 mutant associates with the loading complex when peptide supply is limited. The association of class I molecules with the TAP-associated loading complex appears to be a reflection of how quickly the stable conformation is gained.


Assuntos
Apresentação de Antígeno , Antígeno HLA-A2/química , Antígeno HLA-A2/imunologia , Mutação , Dobramento de Proteína , Membro 2 da Subfamília B de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/metabolismo , Alelos , Sequência de Aminoácidos , Substituição de Aminoácidos/genética , Antiporters/metabolismo , Sítios de Ligação , Proteínas de Ligação ao Cálcio/metabolismo , Calreticulina , Linhagem Celular , Membrana Celular/metabolismo , Retículo Endoplasmático/metabolismo , Antígeno HLA-A2/genética , Antígeno HLA-A2/metabolismo , Humanos , Imunoglobulinas/metabolismo , Cinética , Proteínas de Membrana Transportadoras , Modelos Moleculares , Peptídeos/imunologia , Peptídeos/metabolismo , Testes de Precipitina , Conformação Proteica , Ribonucleoproteínas/metabolismo , Transfecção , Microglobulina beta-2/metabolismo
4.
J Immunol ; 164(2): 833-8, 2000 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-10623829

RESUMO

The T cell coreceptor CD8 exists on mature T cells as disulfide-linked homodimers of CD8 alpha polypeptide chains and heterodimers of CD8 alpha- and CD8 beta-chains. The function of the CD8 alpha-chain for binding to MHC class I and associating with the tyrosine kinase p56lck was demonstrated with CD8 alpha alpha homodimers. CD8 alpha beta functions as a better coreceptor, but the actual function of CD8 beta is less clear. Addressing this issue has been hampered by the apparent inability of CD8 beta to be expressed without CD8 alpha. This study demonstrates that human, but not mouse, CD8 beta can be expressed on the cell surface without CD8 alpha in both transfected COS-7 cells and murine lymphocytes. By creating chimeric proteins, we show that the murine Ig domain of CD8 beta is responsible for the lack of expression of murine CD8 beta beta dimers. In contrast to CD8 alpha alpha, CD8 beta beta is unable to bind MHC class I in a cell-cell adhesion assay. Detection of this form of CD8 should facilitate studies on the function of the CD8 beta-chain and indicates that caution should be used when interpreting studies on CD8 function using chimeric protein with the murine CD8 beta beta Ig domain. In addition, we demonstrate that the Ig domains of CD8 alpha are also involved in controlling the ability of CD8 to be expressed. Mutation of B- and F-strand cysteine residues in CD8 alpha reduced the ability of the protein to fold properly and, therefore, to be expressed.


Assuntos
Antígenos CD8/biossíntese , Antígenos CD8/genética , Animais , Antígenos CD8/metabolismo , Células COS , Linhagem Celular , Cisteína/genética , Cisteína/metabolismo , Dimerização , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Imunoglobulinas/genética , Camundongos , Camundongos Transgênicos , Ligação Proteica/genética , Ligação Proteica/imunologia , Isoformas de Proteínas/biossíntese , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Estrutura Terciária de Proteína/genética , Especificidade da Espécie , Transfecção
5.
Immunol Res ; 19(2-3): 201-10, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10493174

RESUMO

The T cell coreceptor CD8 is a cell-surface glycoprotein expressed either as a disulfide-linked homodimer of two CD8alpha monomers, or a heterodimer of CD8alpha and CD8beta. These receptors interact with ligands, such as major histocompatibility complex (MHC) class I, on the outside of the cell, with proteins inside the cell, such as the tyrosine kinase p56lck, and possibly with proteins on the same cell-surface. The molecular details describing such protein interactions can shed light on how the proteins function and the functional differences between the two forms of CD8. Crystal structures, mutational analysis, affinity measurements, and other approaches are providing those details.


Assuntos
Antígenos CD8/genética , Antígenos CD8/metabolismo , Antígenos de Histocompatibilidade Classe I/metabolismo , Linfócitos T/metabolismo , Animais , Antígenos CD8/química , Humanos , Ligantes , Camundongos , Receptores de Antígenos de Linfócitos T , Transdução de Sinais
6.
J Immunol ; 162(2): 846-51, 1999 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-9916707

RESUMO

The cell surface glycoprotein CD8 functions as a coreceptor with the TCR for interaction with MHC class I. The cocrystal structure of the CD8 alpha alpha-MHC complex showed that one CD8 Ig domain provided the majority of the contact with MHC class I and that residue R4 of that domain contacted the alpha2 domain of MHC class I. We previously showed by mutational analysis that this residue was critical for binding to MHC class I. To determine which of the Ig domains for the CD8 alpha beta heterodimer would make the most contact with class I MHC, we expressed single-chain or dimeric forms of CD8 on COS-7 cells and measured the adhesion of MHC class I positive cells. We found that when one of the R4 residues was mutated in a CD8 alpha alpha homodimer binding comparable to that of wild type was observed, whereas a double R4 mutant severely impaired binding. However, when mutant CD8 alpha (R4K) was coexpressed with wild-type CD8 beta, binding was not observed. These results support the model in which it is CD8 alpha, not CD8 beta, that is making the most of the contact with MHC class I, including the alpha 2 domain. In addition, they demonstrate that a single-chain form of CD8 alpha alpha can bind to MHC class I.


Assuntos
Antígenos CD8/metabolismo , Antígenos de Histocompatibilidade Classe I/metabolismo , Imunoglobulinas/metabolismo , Animais , Sequência de Bases , Sítios de Ligação/genética , Sítios de Ligação/imunologia , Antígenos CD8/química , Antígenos CD8/genética , Células COS , Adesão Celular/imunologia , Dimerização , Antígenos de Histocompatibilidade Classe I/química , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Imunoglobulinas/química , Imunoglobulinas/genética , Modelos Moleculares , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Estrutura Terciária de Proteína , Relação Estrutura-Atividade , Transfecção/imunologia
7.
Nucleic Acids Res ; 26(22): 5228-9, 1998 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-9801325

RESUMO

We developed a marker gene encoding a human cell surface molecule called CD8 for use in transgenic animal studies. The CD8 cDNA contains three mutations: one in the extracellular domain which prevents interaction with its ligand MHC class I and the other two in the cytoplasmic domain which inhibit its signalling function. The cDNA was linked to a fragment of the human growth hormone gene and in transgenic animal studies, expression was observed in the appropriate cell types using a CD2 enhancer. The advantage of the CD8 marker gene is that it is incapable of signalling via its only known signalling pathway and its expression can be monitored using monoclonal antibodies and microscopy or flow cytometry.


Assuntos
Animais Geneticamente Modificados/genética , Antígenos CD8/genética , Marcadores Genéticos , Animais , Animais Geneticamente Modificados/imunologia , Anticorpos Monoclonais , Antígenos CD8/química , DNA Complementar/genética , Expressão Gênica , Vetores Genéticos , Humanos , Linfócitos/imunologia , Mutação
8.
J Immunol ; 159(10): 4907-12, 1997 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-9366416

RESUMO

The human CD8 glycoprotein is expressed either as an alpha beta heterodimer or as an alpha alpha homodimer on thymocytes, mature T cells, and subpopulations of intestinal intraepithelial lymphocytes (IELs). The homodimeric form of CD8 is exclusively expressed on TCR gamma delta IELs and on subsets of NK cells and TCR alpha beta IELs. To understand the molecular mechanisms by which these genes are regulated, we created transgenic mice with a 95-kb human genomic DNA fragment containing the entire CD8 beta gene as well as a cluster of tissue-specific DNase I-hypersensitive sites 7 to 10 kb upstream of the gene. These sites were present in CD8 alpha beta+- but not CD8 alpha beta- T cell lines nor in a B cell line. We found that transgenic mice had correct developmental expression of human CD8 beta on thymocytes and mature CD8+ cells and no expression on mature CD4+ T cells or B cells. Interestingly, the percentage of mouse CD8 alpha+ cells that were human CD8 beta+ varied, depending on the founder line, from 4 to 88%, whereas the percentage among siblings was similar, indicative of a variegated phenotype resulting from site of integration effects. Expression was also observed on intestinal IELs, but only on those expressing the TCR alpha beta receptor and not the TCR gamma delta cells, which exclusively express CD8 alpha alpha. Of the TCR alpha beta+ cells, the transgene was expressed in both the CD8 alpha alpha and alpha beta subpopulations. These results indicate that this 95-kb fragment affords developmentally correct expression of the human CD8 beta gene on thymus-derived T cells in transgenic animals. Therefore, CD8 lineage-specific regulatory sequences must be located within the fragment.


Assuntos
Antígenos CD8/genética , Regulação da Expressão Gênica no Desenvolvimento/imunologia , Camundongos Transgênicos/imunologia , Transgenes/imunologia , Animais , Linfócitos B , Linhagem Celular , Clonagem Molecular , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Linfócitos T , Timo/crescimento & desenvolvimento , Timo/imunologia , Timo/metabolismo , Células Tumorais Cultivadas
9.
J Immunol ; 159(12): 6077-82, 1997 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-9550407

RESUMO

The CD8 molecule is expressed either as an alpha/alpha homodimer or an alpha/beta heterodimer on thymocytes and cytotoxic T cells, and functions as a coreceptor in concert with TCR for binding the MHC class I/peptide complex. Although CD8alpha/beta heterodimers have been shown to be more effective coreceptors, the precise role of the beta-chain in TCR-mediated thymic maturation and T cell activation is not understood. To understand the role of CD8beta in mediating CD8/MHC class I interaction, we examined whether cell surface CD8alpha/beta heterodimer promotes better cell-cell adhesion with MHC class I than the CD8alpha/alpha homodimer. The abilities of different forms of CD8 to adhere to MHC class I were measured with a cell-cell binding assay. Using a wild-type CD8beta and -alpha, we found that CD8alphabeta heterodimers did not mediate greater cell-cell adhesion than CD8alphaalpha homodimers. Furthermore, we found that chimeric CD8beta-alpha homodimers afforded no detectable binding. These results do not support the idea that CD8alphabeta binding to MHC class I is greater than that of CD8alphaalpha. Rather, they point to an alternative explanation in which CD8beta may play an role in promoting CD8/TCR interaction and/or in signaling/regulatory pathways.


Assuntos
Antígenos CD8/fisiologia , Antígenos de Histocompatibilidade Classe I/fisiologia , Animais , Antígenos CD8/biossíntese , Antígenos CD8/genética , Antígenos CD8/metabolismo , Células COS , Adesão Celular/imunologia , Dimerização , Antígenos de Histocompatibilidade Classe I/biossíntese , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Ligação Proteica/imunologia , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/química , Células Tumorais Cultivadas , Microglobulina beta-2/fisiologia
10.
Int Immunol ; 8(10): 1617-26, 1996 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8921442

RESUMO

In our previous work, DNase hypersensitivity mapping was used to identify an enhancer within the human CD8 alpha (hCD8 alpha) gene which allowed T cell-specific expression of a reporter construct in transiently transfected cell lines. To study the role of this intronic enhancer in vivo, transgenic mice were made using human CD8 genomic constructs. We found that while a 14 kb wild-type human CD8 alpha (WThCD8) genomic construct did not lead to expression in mature peripheral CD8+ T cells, this transgene was consistently expressed in small populations of T cells and B cells, and in a subset of mouse NK cells. While murine CD8 is not normally expressed on resting NK cells, expression of the human CD8 transgene on mouse NK cells is appropriate since CD8 is expressed on a subset of human NK cells. Deletion of the intronic enhancer resulted in a complete loss of transgene expression in most lines and a loss of expression only in NK cells in one line. Our results indicate, firstly, that cis-acting sequences within the 14 kb genomic fragment are sufficient for NK cell-specific expression. In addition, our results suggest that the enhancer may have dual roles in regulation of transgene expression. It may enhance general expression of the transgene and may also be required for NK cell-specific expression.


Assuntos
Antígenos CD8/biossíntese , Antígenos CD8/genética , Expressão Gênica/genética , Células Matadoras Naturais/metabolismo , Linfócitos T Citotóxicos/metabolismo , Animais , Humanos , Células Matadoras Ativadas por Linfocina/metabolismo , Células Matadoras Naturais/imunologia , Camundongos , Camundongos Transgênicos , Linfócitos T Citotóxicos/imunologia , Transgenes/imunologia
11.
Immunogenetics ; 45(2): 130-5, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-8952962

RESUMO

Lack of expression of a cell surface protein can occur by means of transcriptional and/or post-transcriptional mechanisms. Expression of the CD8A gene has been shown to be regulated by post-transcriptional mechanisms when 1) CD4(-)CD8(lo) thymocytes are blocked from differentiating into CD4(+)CD8(+) cells by TCR crosslinking and 2) upon activation of mature CD8(+) T cells. We demonstrate in this paper that there is also post-transcriptional regulation of CD8A expression in a CD4(+)CD8(-) T-cell line Jurkat. On the basis of northern blotting, mRNA for CD8A was not seen to be present in the Jurkat cells, but the gene was observed to be transcriptionally active in nuclear run-on analysis. In addition, we provide evidence that post-transcriptional mechanisms also contribute to the regulation of CD8A expression in mature CD4(+)CD8(-) T cells, challenging the assumption that the regulation is due solely to transcriptional mechanisms.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Antígenos CD8/biossíntese , Animais , Antígenos CD8/genética , Humanos , Leucemia-Linfoma de Células T do Adulto/imunologia , Camundongos , Camundongos Transgênicos , RNA Mensageiro/genética , Transcrição Gênica
12.
J Exp Med ; 182(5): 1275-80, 1995 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-7595198

RESUMO

The cell surface glycoprotein CD8 functions as a coreceptor with the TCR on cytotoxic T lymphocytes. Mutational analysis of the binding site of CD8 for MHC class I predicted that distinct surfaces of CD8 would interact with both the alpha 2 and alpha 3 domains of class I. Using a cell-cell adhesion assay, we identified three residues Q115, D122, and E128 in the alpha 2 domain of class I critical for interaction with CD8. The side chains of these residues point towards a cavity formed by the alpha 1/alpha 2 platform, the alpha 3 domain and beta 2-microglobulin (beta 2m) of class I. These residues were predicted to contact CD8 based on a bivalent model of interaction between one CD8 alpha/alpha homodimer and two MHC class I molecules. These results therefore provide support for the model.


Assuntos
Antígenos CD8/metabolismo , Antígeno HLA-A2/metabolismo , Conformação Proteica , Animais , Sítios de Ligação , Células CHO , Adesão Celular , Linhagem Celular , Chlorocebus aethiops , Cricetinae , DNA Complementar/genética , Modelos Moleculares , Mutagênese Sítio-Dirigida , Ligação Proteica , Microglobulina beta-2/metabolismo
13.
Proc Natl Acad Sci U S A ; 91(5): 1716-20, 1994 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-8127870

RESUMO

The CD8 dimer interacts with the alpha 3 domain of major histocompatibility complex class I molecules through two immunoglobulin variable-like domains. In this study a crystal structure-informed mutational analysis has been performed to identify amino acids in the CD8 alpha/alpha homodimer that are likely to be involved in binding to class I. Several key residues are situated on the top face of the dimer within loops analogous to the complementarity-determining regions (CDRs) of immunoglobulin. In addition, other important amino acids are located in the A and B beta-strands on the sides of the dimer. The potential involvement of amino acids on both the top and the side faces of the molecule is consistent with a bivalent model for the interaction between a single CD8 alpha/alpha homodimer and two class I molecules and may have important implications for signal transduction in class I-expressing cells. This study also demonstrates a role for the positive surface potential of CD8 in class I binding and complements previous work demonstrating the importance of a negatively charged loop on the alpha 3 domain of class I for CD8 alpha/alpha-class I interaction. We propose a model whereby residues located on the CDR-like loops of the CD8 homodimer interact with the alpha 3 domain of MHC class I while amino acids on the side of the molecule containing the A and B beta-strands contact the alpha 2 domain of class I.


Assuntos
Antígenos CD8/química , Antígenos de Histocompatibilidade Classe I/metabolismo , Modelos Moleculares , Animais , Linfócitos B/imunologia , Sítios de Ligação , Antígenos CD8/genética , Antígenos CD8/metabolismo , Adesão Celular/imunologia , Linhagem Celular , Eletroquímica , Antígenos HLA/química , Antígenos HLA/metabolismo , Haplorrinos , Antígenos de Histocompatibilidade Classe I/química , Humanos , Mutagênese Sítio-Dirigida , Ligação Proteica , Conformação Proteica
14.
J Immunol ; 150(10): 4376-85, 1993 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-8387094

RESUMO

Expression of the CD8 gene is highly regulated during lymphocyte differentiation and in a tissue-specific manner. We characterized the human CD8 alpha promoter region to determine whether tissue specificity resides within the promoter and to define important regulatory elements. A set of six fragments 5' of the CD8 alpha gene were linked to a luciferase reporter gene. The luciferase activity was then measured in a transient transfection assay. We found that CD8 alpha promoter activity can be detected from a 146-bp fragment upstream of the translation start site, but not from a 133-bp fragment. The cyclic AMP response element (CRE)-like site within the 10 bp from -143 to -133 is critical for promoter activity. Mutation of the CRE/decamer in the context of a 429-bp fragment causes loss of activity. Tissue specificity does not reside in the 146-bp fragment because this fragment directs expression in both T and non-T cell lines. Fragments longer than 146 bp are generally expressed less well in the cell lines suggesting the potential existence of negative regulatory elements upstream of -146. Using a CRE/decamer-containing oligomer as a probe in an electrophoresis mobility shift assay, three retarded bands formed by proteins binding to the DNA were detected using nuclear extracts from two T cell lines. Two of the three bands contain proteins of the CRE-binding protein (CREB)/activating transcription factor (ATF) family. Because the CRE-binding protein/activating transcription factor proteins play a role in the expression of many other T cell-specific genes, our work strengthens the hypothesis that the CRE motif is important for regulating the expression of T cell-specific genes.


Assuntos
Antígenos CD8/genética , AMP Cíclico/fisiologia , Regiões Promotoras Genéticas , Linfócitos T/fisiologia , Sequência de Bases , Sítios de Ligação , Sequência Consenso , Regulação da Expressão Gênica , Humanos , Técnicas In Vitro , Dados de Sequência Molecular , Proteínas Nucleares/metabolismo , Oligodesoxirribonucleotídeos/química , RNA Mensageiro/genética , Sequências Reguladoras de Ácido Nucleico , Fatores de Transcrição/metabolismo , Células Tumorais Cultivadas
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