Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 13 de 13
Filtrar
Filtros adicionais











Intervalo de ano
1.
Artigo em Inglês | MEDLINE | ID: mdl-31484767

RESUMO

Juvenile-onset recurrent respiratory papillomatosis (JRRP) is a rare and debilitating childhood disease that presents with recurrent growth of papillomas in the upper airway. Two common human papillomaviruses (HPVs), HPV-6 and -11, are implicated in most cases, but it is still not understood why only a small proportion of children develop JRRP following exposure to these common viruses. We report 2 siblings with a syndromic form of JRRP associated with mild dermatologic abnormalities. Whole-exome sequencing of the patients revealed a private homozygous mutation in NLRP1, encoding Nucleotide-Binding Domain Leucine-Rich Repeat Family Pyrin Domain-Containing 1. We find the NLRP1 mutant allele to be gain of function (GOF) for inflammasome activation, as demonstrated by the induction of inflammasome complex oligomerization and IL-1ß secretion in an overexpression system. Moreover, patient-derived keratinocytes secrete elevated levels of IL-1ß at baseline. Finally, both patients displayed elevated levels of inflammasome-induced cytokines in the serum. Six NLRP1 GOF mutations have previously been described to underlie 3 allelic Mendelian diseases with differing phenotypes and modes of inheritance. Our results demonstrate that an autosomal recessive, syndromic form of JRRP can be associated with an NLRP1 GOF mutation.

2.
J Exp Med ; 216(9): 2057-2070, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31270247

RESUMO

Vaccination against measles, mumps, and rubella (MMR) and yellow fever (YF) with live attenuated viruses can rarely cause life-threatening disease. Severe illness by MMR vaccines can be caused by inborn errors of type I and/or III interferon (IFN) immunity (mutations in IFNAR2, STAT1, or STAT2). Adverse reactions to the YF vaccine have remained unexplained. We report two otherwise healthy patients, a 9-yr-old boy in Iran with severe measles vaccine disease at 1 yr and a 14-yr-old girl in Brazil with viscerotropic disease caused by the YF vaccine at 12 yr. The Iranian patient is homozygous and the Brazilian patient compound heterozygous for loss-of-function IFNAR1 variations. Patient-derived fibroblasts are susceptible to viruses, including the YF and measles virus vaccine strains, in the absence or presence of exogenous type I IFN. The patients' fibroblast phenotypes are rescued with WT IFNAR1 Autosomal recessive, complete IFNAR1 deficiency can result in life-threatening complications of vaccination with live attenuated measles and YF viruses in previously healthy individuals.

3.
J Exp Med ; 216(8): 1777-1790, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31213488

RESUMO

Fulminant viral hepatitis (FVH) is a devastating and unexplained condition that strikes otherwise healthy individuals during primary infection with common liver-tropic viruses. We report a child who died of FVH upon infection with hepatitis A virus (HAV) at age 11 yr and who was homozygous for a private 40-nucleotide deletion in IL18BP, which encodes the IL-18 binding protein (IL-18BP). This mutation is loss-of-function, unlike the variants found in a homozygous state in public databases. We show that human IL-18 and IL-18BP are both secreted mostly by hepatocytes and macrophages in the liver. Moreover, in the absence of IL-18BP, excessive NK cell activation by IL-18 results in uncontrolled killing of human hepatocytes in vitro. Inherited human IL-18BP deficiency thus underlies fulminant HAV hepatitis by unleashing IL-18. These findings provide proof-of-principle that FVH can be caused by single-gene inborn errors that selectively disrupt liver-specific immunity. They also show that human IL-18 is toxic to the liver and that IL-18BP is its antidote.

4.
J Exp Med ; 215(10): 2567-2585, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30143481

RESUMO

Life-threatening pulmonary influenza can be caused by inborn errors of type I and III IFN immunity. We report a 5-yr-old child with severe pulmonary influenza at 2 yr. She is homozygous for a loss-of-function IRF9 allele. Her cells activate gamma-activated factor (GAF) STAT1 homodimers but not IFN-stimulated gene factor 3 (ISGF3) trimers (STAT1/STAT2/IRF9) in response to IFN-α2b. The transcriptome induced by IFN-α2b in the patient's cells is much narrower than that of control cells; however, induction of a subset of IFN-stimulated gene transcripts remains detectable. In vitro, the patient's cells do not control three respiratory viruses, influenza A virus (IAV), parainfluenza virus (PIV), and respiratory syncytial virus (RSV). These phenotypes are rescued by wild-type IRF9, whereas silencing IRF9 expression in control cells increases viral replication. However, the child has controlled various common viruses in vivo, including respiratory viruses other than IAV. Our findings show that human IRF9- and ISGF3-dependent type I and III IFN responsive pathways are essential for controlling IAV.

5.
Eur J Med Genet ; 60(8): 426-432, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28576691

RESUMO

BACKGROUND: Acute liver failure (ALF) in children can be life-threatening. Although many causes are known, ALF remains unexplained in about half of the cases. Recently, bi-allelic mutations in NBAS were reported to underlie recurrent episodes of elevated liver transaminases (ELT) and ALF in the context of diverse extrahepatic phenotypes. METHODS AND RESULTS: We here describe two sisters, born to non-consanguineous Portuguese parents, who had short stature and presented with recurrent episodes of severe ELT triggered by febrile respiratory viral infections since early childhood. Patient 1 had mild facial dysmorphism and died during the second ELT crisis at 3-11/12 years of age. Patient 2, currently 9 years old, had multiple episodes of ELT (>30), twice with ALF, often accompanied by extensive urticaria and facial angioedema. Whole-exome and Sanger sequencing revealed that both patients carried previously undescribed compound heterozygous mutations of NBAS (NM_015909.3): c.680A > C (p.His227Pro), affecting an evolutionarily conserved residue, and c.1749G > A (p.Trp583*), causing a premature stop codon. Both mutations are predicted to be highly damaging. The parents and two younger siblings are healthy and heterozygous for one or another mutant allele. CONCLUSION: The multiplex kindred reported herein expands the genotypic and phenotypic spectrum of this recently described clinical syndrome due to autosomal recessive NBAS deficiency.


Assuntos
Falência Hepática Aguda/genética , Mutação de Sentido Incorreto , Proteínas de Neoplasias/genética , Transaminases/metabolismo , Adulto , Alelos , Criança , Pré-Escolar , Códon de Terminação , Feminino , Humanos , Fígado/enzimologia , Fígado/patologia , Falência Hepática Aguda/diagnóstico , Masculino , Linhagem , Irmãos
6.
J Am Coll Cardiol ; 69(13): 1653-1665, 2017 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-28359509

RESUMO

BACKGROUND: Myocarditis is inflammation of the heart muscle that can follow various viral infections. Why children only rarely develop life-threatening acute viral myocarditis (AVM), given that the causal viral infections are common, is unknown. Genetic lesions might underlie such susceptibilities. Mouse genetic studies demonstrated that interferon (IFN)-α/ß immunity defects increased susceptibility to virus-induced myocarditis. Moreover, variations in human TLR3, a potent inducer of IFNs, were proposed to underlie AVM. OBJECTIVES: This study sought to evaluate the hypothesis that human genetic factors may underlie AVM in previously healthy children. METHODS: We tested the role of TLR3-IFN immunity using human induced pluripotent stem cell-derived cardiomyocytes. We then performed whole-exome sequencing of 42 unrelated children with acute myocarditis (AM), some with proven viral causes. RESULTS: We found that TLR3- and STAT1-deficient cardiomyocytes were not more susceptible to Coxsackie virus B3 (CVB3) infection than control cells. Moreover, CVB3 did not induce IFN-α/ß and IFN-α/ß-stimulated genes in control cardiomyocytes. Finally, exogenous IFN-α did not substantially protect cardiomyocytes against CVB3. We did not observe a significant enrichment of rare variations in TLR3- or IFN-α/ß-related genes. Surprisingly, we found that homozygous but not heterozygous rare variants in genes associated with inherited cardiomyopathies were significantly enriched in AM-AVM patients compared with healthy individuals (p = 2.22E-03) or patients with other diseases (p = 1.08E-04). Seven of 42 patients (16.7%) carried rare biallelic (homozygous or compound heterozygous) nonsynonymous or splice-site variations in 6 cardiomyopathy-associated genes (BAG3, DSP, PKP2, RYR2, SCN5A, or TNNI3). CONCLUSIONS: Previously silent recessive defects of the myocardium may predispose to acute heart failure presenting as AM, notably after common viral infections in children.


Assuntos
Cardiomiopatias/genética , Enterovirus Humano B/fisiologia , Miocardite/genética , Fator de Transcrição STAT1/genética , Receptor 3 Toll-Like/genética , Cardiomiopatias/complicações , Estudos de Casos e Controles , Feminino , Interações Hospedeiro-Patógeno/genética , Humanos , Células-Tronco Pluripotentes Induzidas , Masculino , Miocardite/virologia , Miócitos Cardíacos/virologia
7.
PLoS One ; 9(1): e85274, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24416377

RESUMO

Physiological stress resulting from infections, trauma, surgery, alcoholism, malnutrition, and/or pregnancy results in a substantial depletion of immature CD4(+)CD8(+) thymocytes. We previously identified 18 distinct stress-responsive microRNAs (miRs) in the thymus upon systemic stress induced by lipopolysaccharide (LPS) or the synthetic glucocorticoid, dexamethasone (Dex). MiRs are short, non-coding RNAs that play critical roles in the immune system by targeting diverse mRNAs, suggesting that their modulation in the thymus in response to stress could impact thymopoiesis. MiR-181d is one such stress-responsive miR, exhibiting a 15-fold down-regulation in expression. We utilized both transgenic and gene-targeting approaches to study the impact of miR-181d on thymopoiesis under normal and stress conditions. The over-expression of miR-181d in developing thymocytes reduced the total number of immature CD4(+)CD8(+) thymocytes. LPS or Dex injections caused a 4-fold greater loss of these cells when compared with the wild type controls. A knockout mouse was developed to selectively eliminate miR-181d, leaving the closely spaced and contiguous family member miR-181c intact. The targeted elimination of just miR-181d resulted in a thymus stress-responsiveness similar to wild-type mice. These experiments suggest that one or more of three other miR-181 family members have overlapping or compensatory functions. Gene expression comparisons of thymocytes from the wild type versus transgenic mice indicated that miR-181d targets a number of stress, metabolic, and signaling pathways. These findings demonstrate that selected miRs enhance stress-mediated thymic involution in vivo.


Assuntos
MicroRNAs/genética , Timócitos/metabolismo , Timo/metabolismo , Animais , Sequência de Bases , Antígenos CD4/genética , Antígenos CD4/imunologia , Antígenos CD8/genética , Antígenos CD8/imunologia , Dexametasona/farmacologia , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Transgênicos , MicroRNAs/imunologia , Dados de Sequência Molecular , Cultura Primária de Células , Estresse Fisiológico , Timócitos/efeitos dos fármacos , Timócitos/imunologia , Timo/efeitos dos fármacos , Timo/imunologia
8.
J Biol Chem ; 288(42): 30752-62, 2013 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-24014023

RESUMO

miR-185 is a microRNA (miR) that targets Bruton's tyrosine kinase in B cells, with reductions in miR-185 linked to B cell autoantibody production. In hippocampal neurons, miR-185 targets both sarcoplasmic/endoplasmic reticulum calcium ATPase 2 and a novel Golgi inhibitor. This miR is haploinsufficient in 90-95% of individuals with chromosome 22q11.2 deletion syndrome, patients who can present with immune, cardiac, and parathyroid problems, learning disorders, and a high incidence of schizophrenia in adults. The reduced levels of miR-185 in neurons cause presynaptic neurotransmitter release. Many of the 22q11.2 deletion syndrome patients have a thymic hypoplasia, which results in a peripheral T cell lymphopenia and unusual T helper cell skewing. The molecular targets of miR-185 in thymocytes are unknown. Using an miR-185 T cell transgenic approach, increasing levels of miR-185 attenuated T cell development at the T cell receptor ß (TCRß) selection checkpoint and during positive selection. This caused a peripheral T cell lymphopenia. Mzb1, Nfatc3, and Camk4 were identified as novel miR-185 targets. Elevations in miR-185 enhanced TCR-dependent intracellular calcium levels, whereas a knockdown of miR-185 diminished these calcium responses. These effects concur with reductions in Mzb1, an endoplasmic reticulum calcium regulator. Consistent with their haploinsufficiency of miR-185, Mzb1 levels were elevated in thymocyte extracts from several 22q11.2 deletion syndrome patients. Our findings indicate that miR-185 regulates T cell development through its targeting of several mRNAs including Mzb1.


Assuntos
Sinalização do Cálcio , Citocinas/biossíntese , MicroRNAs/biossíntese , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Timócitos/metabolismo , Animais , Cálcio/imunologia , Cálcio/metabolismo , Proteína Quinase Tipo 4 Dependente de Cálcio-Calmodulina/genética , Proteína Quinase Tipo 4 Dependente de Cálcio-Calmodulina/imunologia , Proteína Quinase Tipo 4 Dependente de Cálcio-Calmodulina/metabolismo , Citocinas/genética , Citocinas/imunologia , Humanos , Camundongos , Camundongos Transgênicos , MicroRNAs/genética , MicroRNAs/imunologia , Fatores de Transcrição NFATC/genética , Fatores de Transcrição NFATC/imunologia , Fatores de Transcrição NFATC/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/imunologia , RNA Mensageiro/metabolismo , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Timócitos/citologia , Timócitos/imunologia , Transgenes/genética , Transgenes/imunologia
9.
Clin Immunol ; 147(1): 11-22, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23454892

RESUMO

Patients with 22q11.2 deletion syndrome have heterogeneous clinical presentations including immunodeficiency, cardiac anomalies, and hypocalcemia. The syndrome arises from hemizygous deletions of up to 3Mb on chromosome 22q11.2, a region that contains 60 genes and 4 microRNAs. MicroRNAs are important post-transcriptional regulators of gene expression, with mutations in several microRNAs causal to specific human diseases. We characterized the microRNA expression patterns in the peripheral blood of patients with 22q11.2 deletion syndrome (n=31) compared to normal controls (n=22). Eighteen microRNAs had a statistically significant differential expression (p<0.05), with miR-185 expressed at 0.4× normal levels. The 22q11.2 deletion syndrome cohort exhibited microRNA expression hyper-variability and group dysregulation. Selected microRNAs distinguished patients with cardiac anomalies, hypocalcemia, and/or low circulating T cell counts. In summary, microRNA profiling of chromosome 22q11.2 deletion syndrome/DiGeorge patients revealed a signature microRNA expression pattern distinct from normal controls with clinical relevance.


Assuntos
Síndrome de DiGeorge/genética , Perfilação da Expressão Gênica , MicroRNAs/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Adolescente , Criança , Pré-Escolar , Deleção Cromossômica , Cromossomos Humanos Par 22/genética , Estudos de Coortes , Feminino , Cardiopatias Congênitas/genética , Humanos , Hipocalcemia/genética , Lactente , Contagem de Linfócitos , Masculino , Linfócitos T/metabolismo
10.
PLoS One ; 7(11): e50396, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23226274

RESUMO

CD81 (TAPA-1) is a ubiquitously expressed tetraspanin protein identified as a component of the B lymphocyte receptor (BCR) and as a receptor for the Hepatitis C Virus. In an effort to identify trans-membrane proteins that interact with the T-cell antigen receptor (TCR), we performed a membrane yeast two hybrid screen and identified CD81 as an interactor of the CD3delta subunit of the TCR. We found that in the absence of CD81, in thymocytes from knockout mice, TCR engagement resulted in stronger signals. These results were recapitulated in T cell lines that express low levels of CD81 through shRNA mediated silencing. Increased signaling did not result from alterations in the levels of TCR on the surface of T lymphocytes. Although CD81 is not essential for normal T lymphocyte development, it plays an important role in regulating TCR and possibly pre-TCR signal transduction by controlling the strength of signaling. CD81 dependent alterations in thymocyte signaling are evident in increased CD5 expression on CD81 deficient double positive (DP) thymocytes. We conclude that CD81 interacts with the T cell receptor to suppress signaling.


Assuntos
Receptores de Antígenos de Linfócitos T gama-delta/genética , Transdução de Sinais/genética , Tetraspanina 28/genética , Animais , Antígenos CD5/genética , Antígenos CD5/imunologia , Comunicação Celular , Expressão Gênica , Células HEK293 , Humanos , Ativação Linfocitária , Camundongos , Camundongos Knockout , Plasmídeos , Ligação Proteica , RNA Interferente Pequeno/genética , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Transdução de Sinais/imunologia , Tetraspanina 28/antagonistas & inibidores , Tetraspanina 28/imunologia , Timócitos/citologia , Timócitos/metabolismo , Transfecção , Técnicas do Sistema de Duplo-Híbrido
11.
Antimicrob Agents Chemother ; 56(9): 4806-15, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22751536

RESUMO

We hypothesize that low-level efflux pump expression is the first step in the development of high-level drug resistance in mycobacteria. We performed 28-day azithromycin dose-effect and dose-scheduling studies in our hollow-fiber model of disseminated Mycobacterium avium-M. intracellulare complex. Both microbial kill and resistance emergence were most closely linked to the within-macrophage area under the concentration-time curve (AUC)/MIC ratio. Quantitative PCR revealed that subtherapeutic azithromycin exposures over 3 days led to a 56-fold increase in expression of MAV_3306, which encodes a putative ABC transporter, and MAV_1406, which encodes a putative major facilitator superfamily pump, in M. avium. By day 7, a subpopulation of M. avium with low-level resistance was encountered and exhibited the classic inverted U curve versus AUC/MIC ratios. The resistance was abolished by an efflux pump inhibitor. While the maximal microbial kill started to decrease after day 7, a population with high-level azithromycin resistance appeared at day 28. This resistance could not be reversed by efflux pump inhibitors. Orthologs of pumps encoded by MAV_3306 and MAV_1406 were identified in Mycobacterium tuberculosis, Mycobacterium leprae, Mycobacterium marinum, Mycobacterium abscessus, and Mycobacterium ulcerans. All had highly conserved protein secondary structures. We propose that induction of several efflux pumps is the first step in a general pathway to drug resistance that eventually leads to high-level chromosomal-mutation-related resistance in mycobacteria as ordered events in an "antibiotic resistance arrow of time."


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Antituberculosos/farmacologia , Azitromicina/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Proteínas Fúngicas/genética , Mycobacterium avium/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Sequência de Aminoácidos , Área Sob a Curva , Sequência Conservada , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/microbiologia , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Mycobacterium avium/efeitos dos fármacos , Mycobacterium avium/metabolismo , Reação em Cadeia da Polimerase , Estrutura Secundária de Proteína , Alinhamento de Sequência , Fatores de Tempo
12.
PLoS One ; 6(11): e27580, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22110677

RESUMO

BACKGROUND: Physiological stress evokes rapid changes in both the innate and adaptive immune response. Immature αß T cells developing in the thymus are particularly sensitive to stress, with infections and/or exposure to lipopolysaccharide or glucocorticoids eliciting a rapid apoptotic program. MicroRNAs are a class of small, non-coding RNAs that regulate global gene expression by targeting diverse mRNAs for degradation. We hypothesized that a subset of thymically encoded microRNAs would be stress responsive and modulate thymopoiesis. We performed microRNA profiling of thymic microRNAs isolated from control or stressed thymic tissue obtained from mice. We identified 18 microRNAs that are dysregulated >1.5-fold in response to lipopolysaccharide or the synthetic corticosteroid dexamethasone. These included the miR-17-90 cluster, which have anti-apoptotic functions, and the miR-181 family, which contribute to T cell tolerance. The stress-induced changes in the thymic microRNAs are dynamically and distinctly regulated in the CD4(-)CD8(-), CD4(+)CD8(+), CD4(+)CD8(-), and CD4(-)CD8(+) thymocyte subsets. Several of the differentially regulated murine thymic miRs are also stress responsive in the heart, kidney, liver, brain, and/or spleen. The most dramatic thymic microRNA down modulated is miR-181d, exhibiting a 15-fold reduction following stress. This miR has both similar and distinct gene targets as miR-181a, another member of miR-181 family. Many of the differentially regulated microRNAs have known functions in thymopoiesis, indicating that their dysregulation will alter T cell repertoire selection and the formation of naïve T cells. This data has implications for clinical treatments involving anti-inflammatory steroids, ablation therapies, and provides mechanistic insights into the consequences of infections.


Assuntos
MicroRNAs/genética , MicroRNAs/metabolismo , Estresse Fisiológico/genética , Timo/metabolismo , Animais , Apoptose/efeitos dos fármacos , Sequência de Bases , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/metabolismo , Antígenos CD8/metabolismo , Proliferação de Células/efeitos dos fármacos , Dexametasona/farmacologia , Regulação para Baixo/efeitos dos fármacos , Genes Reporter/genética , Humanos , Fator Inibidor de Leucemia/genética , Lipopolissacarídeos/farmacologia , Luciferases/genética , Masculino , Camundongos , Especificidade de Órgãos , Estresse Fisiológico/efeitos dos fármacos , Timócitos/citologia , Timócitos/efeitos dos fármacos , Timócitos/metabolismo , Timo/citologia , Timo/efeitos dos fármacos , Timo/fisiologia , Fatores de Tempo , Transcriptoma/efeitos dos fármacos
13.
J Immunol ; 186(12): 6839-47, 2011 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-21543646

RESUMO

T cell activation involves a cascade of TCR-mediated signals that are regulated by three distinct intracellular signaling motifs located within the cytoplasmic tails of the CD3 chains. Whereas all the CD3 subunits possess at least one ITAM, the CD3 ε subunit also contains a proline-rich sequence and a basic-rich stretch (BRS). The CD3 ε BRS complexes selected phosphoinositides, interactions that are required for normal cell surface expression of the TCR. The cytoplasmic domain of CD3 ζ also contains several clusters of arginine and lysine residues. In this study, we report that these basic amino acids enable CD3 ζ to complex the phosphoinositides PtdIns(3)P, PtdIns(4)P, PtdIns(5)P, PtdIns(3,5)P(2), and PtdIns(3,4,5)P(3) with high affinity. Early TCR signaling pathways were unaffected by the targeted loss of the phosphoinositide-binding functions of CD3 ζ. Instead, the elimination of the phosphoinositide-binding function of CD3 ζ significantly impaired the ability of this invariant chain to accumulate stably at the immunological synapse during T cell-APC interactions. Without its phosphoinositide-binding functions, CD3 ζ was concentrated in intracellular structures after T cell activation. Such findings demonstrate a novel functional role for CD3 ζ BRS-phosphoinositide interactions in supporting T cell activation.


Assuntos
Complexo CD3/metabolismo , Sinapses Imunológicas , Fosfatidilinositóis/metabolismo , Complexo Receptor-CD3 de Antígeno de Linfócitos T/metabolismo , Aminoácidos Básicos , Animais , Sítios de Ligação/imunologia , Complexo CD3/química , Complexo CD3/imunologia , Linhagem Celular , Humanos , Ativação Linfocitária/imunologia , Camundongos , Fosfatidilinositóis/imunologia , Ligação Proteica/imunologia , Transdução de Sinais/imunologia , Transfecção
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA