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1.
Blood ; 120(24): 4772-82, 2012 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-22993390

RESUMO

Lymphatic endothelial cells (LECs) induce peripheral tolerance by direct presentation to CD8 T cells (T(CD8)). We demonstrate that LECs mediate deletion only via programmed cell death-1 (PD-1) ligand 1, despite expressing ligands for the CD160, B- and T-lymphocyte attenuator, and lymphocyte activation gene-3 inhibitory pathways. LECs induce activation and proliferation of T(CD8), but lack of costimulation through 4-1BB leads to rapid high-level expression of PD-1, which in turn inhibits up-regulation of the high-affinity IL-2 receptor that is necessary for T(CD8) survival. Rescue of tyrosinase-specific T(CD8) by interference with PD-1 or provision of costimulation results in autoimmune vitiligo, demonstrating that LECs are significant, albeit suboptimal, antigen-presenting cells. Because LECs express numerous peripheral tissue antigens, lack of costimulation coupled to rapid high-level up-regulation of inhibitory receptors may be generally important in systemic peripheral tolerance.


Assuntos
Antígeno B7-H1/imunologia , Linfócitos T CD8-Positivos/imunologia , Células Endoteliais/imunologia , Tolerância Imunológica/imunologia , Receptor de Morte Celular Programada 1/imunologia , Transferência Adotiva , Animais , Células Apresentadoras de Antígenos/imunologia , Células Apresentadoras de Antígenos/metabolismo , Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , Doenças Autoimunes/metabolismo , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Células Endoteliais/metabolismo , Linfonodos/imunologia , Linfonodos/metabolismo , Vasos Linfáticos/citologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Microscopia de Fluorescência , Monofenol Mono-Oxigenase/genética , Monofenol Mono-Oxigenase/imunologia , Monofenol Mono-Oxigenase/metabolismo , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/metabolismo , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores OX40/imunologia , Receptores OX40/metabolismo , Transdução de Sinais/imunologia , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/imunologia , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo , Vitiligo/genética , Vitiligo/imunologia , Vitiligo/metabolismo
2.
J Exp Med ; 204(6): 1475-85, 2007 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-17548520

RESUMO

The deubiquitinating enzyme CYLD has recently been implicated in the regulation of signal transduction, but its physiological function and mechanism of action are still elusive. In this study, we show that CYLD plays a pivotal role in regulating T cell activation and homeostasis. T cells derived from Cyld knockout mice display a hyperresponsive phenotype and mediate the spontaneous development of intestinal inflammation. Interestingly, CYLD targets a ubiquitin-dependent kinase, transforming growth factor-beta-activated kinase 1 (Tak1), and inhibits its ubiquitination and autoactivation. Cyld-deficient T cells exhibit constitutively active Tak1 and its downstream kinases c-Jun N-terminal kinase and IkappaB kinase beta. These results emphasize a critical role for CYLD in preventing spontaneous activation of the Tak1 axis of T cell signaling and, thereby, maintaining normal T cell function.


Assuntos
Cisteína Endopeptidases/metabolismo , Ativação Linfocitária/imunologia , MAP Quinase Quinase Quinases/metabolismo , Transdução de Sinais/imunologia , Linfócitos T/metabolismo , Transferência Adotiva , Animais , Enzima Desubiquitinante CYLD , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Imuno-Histoquímica , Camundongos , Camundongos Knockout , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Linfócitos T/imunologia , Ubiquitinação/imunologia
3.
PLoS Pathog ; 5(5): e1000457, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19478869

RESUMO

Virus-specific CD8(+) T cells (T(CD8+)) are initially triggered by peptide-MHC Class I complexes on the surface of professional antigen presenting cells (pAPC). Peptide-MHC complexes are produced by two spatially distinct pathways during virus infection. Endogenous antigens synthesized within virus-infected pAPC are presented via the direct-presentation pathway. Many viruses have developed strategies to subvert direct presentation. When direct presentation is blocked, the cross-presentation pathway, in which antigen is transferred from virus-infected cells to uninfected pAPC, is thought to compensate and allow the generation of effector T(CD8+). Direct presentation of vaccinia virus (VACV) antigens driven by late promoters does not occur, as an abortive infection of pAPC prevents production of these late antigens. This lack of direct presentation results in a greatly diminished or ablated T(CD8+) response to late antigens. We demonstrate that late poxvirus antigens do not enter the cross-presentation pathway, even when identical antigens driven by early promoters access this pathway efficiently. The mechanism mediating this novel means of viral modulation of antigen presentation involves the sequestration of late antigens within virus factories. Early antigens and cellular antigens are cross-presented from virus-infected cells, as are late antigens that are targeted to compartments outside of the virus factories. This virus-mediated blockade specifically targets the cross-presentation pathway, since late antigen that is not cross-presented efficiently enters the MHC Class II presentation pathway. These data are the first to describe an evasion mechanism employed by pathogens to prevent entry into the cross-presentation pathway. In the absence of direct presentation, this evasion mechanism leads to a complete ablation of the T(CD8+) response and a potential replicative advantage for the virus. Such mechanisms of viral modulation of antigen presentation must also be taken into account during the rational design of antiviral vaccines.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Apresentação Cruzada/imunologia , Vaccinia virus/imunologia , Animais , Apresentação de Antígeno , Células Apresentadoras de Antígenos/imunologia , Antígenos Virais/imunologia , Linfócitos T CD8-Positivos/virologia , Linhagem Celular , Antígenos de Histocompatibilidade Classe I , Antígenos de Histocompatibilidade Classe II , Humanos
4.
Immunology ; 125(4): 480-91, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18489571

RESUMO

CD8(+) T cells (T(CD8+)) differentiate into effector cells following recognition of specific peptide-major histocompatibility complex (MHC) class I complexes (pMHC-I) on the surface of professional APCs (pAPCs), such as dendritic cells. Antigenic pMHC-I can be generated from two spatially distinct sources. The direct presentation pathway involves generation of peptide from protein substrate synthesized within the cell that is presenting the pMHC-I. Alternatively, the cross presentation pathway involves presentation of antigen that is not synthesized within the presenting cell, but is derived from exogenous proteins synthesized within other donor cells. The mechanisms by which cross presentation of exogenous antigens occur in vivo remain controversial. The C-type lectin scavenger receptor A (SR-A) has been implicated in a number of potential cross presentation pathways, including the presentation of peptide bound to heat shock proteins, such as glycoprotein 96 (gp96), and the transfer of pMHC-I from a donor cell to the pAPC. We demonstrate here that initiation of T(CD8+) responses is normal in mice lacking SR-A, and that the redundancy of ligand binding exhibited by the SR family is likely to be an important mechanism that ensures cross presentation in vivo. These observations emphasize the requirement to target multiple receptors and antigen-processing pathways during the rational design of vaccines aimed at eliciting protective T(CD8+).


Assuntos
Linfócitos T CD8-Positivos/imunologia , Células Dendríticas/imunologia , Glicoproteínas de Membrana/metabolismo , Receptores Depuradores Classe A/metabolismo , Transferência Adotiva/métodos , Animais , Apresentação de Antígeno , Calreticulina/imunologia , Linhagem Celular , Apresentação Cruzada , Eletroporação , Feminino , Antígenos de Histocompatibilidade Classe I , Memória Imunológica , Interferon gama/imunologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Orthomyxoviridae/imunologia , Ovalbumina , Receptores de Antígenos de Linfócitos T/genética , Receptores Depuradores Classe A/genética , Vaccinia virus/imunologia
5.
Cancer Immunol Res ; 5(12): 1062-1073, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29097419

RESUMO

Although CD8+ T cells are critical for controlling tumors, how they are recruited and home to primary and metastatic lesions is incompletely understood. We characterized the homing receptor (HR) ligands on tumor vasculature to determine what drives their expression and their role in T-cell entry. The anatomic location of B16-OVA tumors affected the expression of E-selectin, MadCAM-1, and VCAM-1, whereas the HR ligands CXCL9 and ICAM-1 were expressed on the vasculature regardless of location. VCAM-1 and CXCL9 expression was induced by IFNγ-secreting adaptive immune cells. VCAM-1 and CXCL9/10 enabled CD8+ T-cell effectors expressing α4ß1 integrin and CXCR3 to enter both subcutaneous and peritoneal tumors, whereas E-selectin enabled E-selectin ligand+ effectors to enter subcutaneous tumors. However, MadCAM-1 did not mediate α4ß7+ effector entry into peritoneal tumors due to an unexpected lack of luminal expression. These data establish the relative importance of certain HRs expressed on activated effectors and certain HR ligands expressed on tumor vasculature in the effective immune control of tumors. Cancer Immunol Res; 5(12); 1062-73. ©2017 AACR.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias/etiologia , Neoplasias/patologia , Neovascularização Patológica/genética , Neovascularização Patológica/imunologia , Imunidade Adaptativa , Animais , Biomarcadores , Linhagem Celular Tumoral , Quimiocina CXCL9/genética , Selectina E/genética , Selectina E/metabolismo , Integrina alfa4beta1/genética , Ligantes , Melanoma Experimental , Camundongos , Modelos Biológicos , Receptores de Retorno de Linfócitos/metabolismo , Molécula 1 de Adesão de Célula Vascular/genética
6.
Nat Commun ; 6: 6771, 2015 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-25857745

RESUMO

Lymphatic endothelial cells (LECs) directly express peripheral tissue antigens and induce CD8 T-cell deletional tolerance. LECs express MHC-II molecules, suggesting they might also tolerize CD4 T cells. We demonstrate that when ß-galactosidase (ß-gal) is expressed in LECs, ß-gal-specific CD8 T cells undergo deletion via the PD-1/PD-L1 and LAG-3/MHC-II pathways. In contrast, LECs do not present endogenous ß-gal in the context of MHC-II molecules to ß-gal-specific CD4 T cells. Lack of presentation is independent of antigen localization, as membrane-bound haemagglutinin and I-Eα are also not presented by MHC-II molecules. LECs express invariant chain and cathepsin L, but not H2-M, suggesting that they cannot load endogenous antigenic peptides onto MHC-II molecules. Importantly, LECs transfer ß-gal to dendritic cells, which subsequently present it to induce CD4 T-cell anergy. Therefore, LECs serve as an antigen reservoir for CD4 T-cell tolerance, and MHC-II molecules on LECs are used to induce CD8 T-cell tolerance via LAG-3.


Assuntos
Apresentação de Antígeno/genética , Antígenos CD/imunologia , Linfócitos T CD4-Positivos/imunologia , Células Dendríticas/imunologia , Células Endoteliais/imunologia , Tolerância Periférica/genética , Animais , Antígenos/genética , Antígenos/imunologia , Antígenos CD/genética , Antígenos de Diferenciação de Linfócitos B/genética , Antígenos de Diferenciação de Linfócitos B/imunologia , Antígeno B7-H1/genética , Antígeno B7-H1/imunologia , Células da Medula Óssea/citologia , Células da Medula Óssea/imunologia , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Catepsina L/genética , Catepsina L/imunologia , Anergia Clonal/genética , Células Dendríticas/citologia , Células Endoteliais/citologia , Expressão Gênica , Hemaglutininas/genética , Hemaglutininas/imunologia , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Cultura Primária de Células , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/imunologia , Transdução de Sinais , beta-Galactosidase/genética , beta-Galactosidase/imunologia , Proteína do Gene 3 de Ativação de Linfócitos
7.
Artigo em Inglês | MEDLINE | ID: mdl-25580369

RESUMO

Lymphatic endothelial cells are most often thought of as structural cells that form the lymphatic vasculature, which transports fluid out of peripheral tissues and transports antigens and antigen presenting cells to lymph nodes. Recently, it has been shown that lymphatic endothelial cells also dynamically respond to and influence the immune response in several ways. Here, we describe how lymphatic endothelial cells induce peripheral T-cell tolerance and how this relates to tolerance induced by other types of antigen presenting cells. Furthermore, the ability of lymphatic endothelial cells to alter immune responses under steady-state or inflammatory conditions is explored, and the therapeutic potential of bypassing lymphatic endothelial cell-induced tolerance to enhance cancer immunotherapy is discussed.

8.
PLoS One ; 9(2): e87740, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24503860

RESUMO

Peripheral self-tolerance eliminates lymphocytes specific for tissue-specific antigens not encountered in the thymus. Recently, we demonstrated that lymphatic endothelial cells in mice directly express peripheral tissue antigens, including tyrosinase, and induce deletion of specific CD8 T cells via Programmed Death Ligand-1 (PD-L1). Here, we demonstrate that high-level expression of peripheral tissue antigens and PD-L1 is confined to lymphatic endothelial cells in lymph nodes, as opposed to tissue (diaphragm and colon) lymphatics. Lymphatic endothelial cells in the lymph node medullary sinus express the highest levels of peripheral tissue antigens and PD-L1, and are the only subpopulation that expresses tyrosinase epitope. The representation of lymphatic endothelial cells in the medullary sinus expressing high-level PD-L1, which is necessary for normal CD8 T cell deletion kinetics, is controlled by lymphotoxin-ß receptor signaling and B cells. Lymphatic endothelial cells from neonatal mice do not express high-level PD-L1 or present tyrosinase epitope. This work uncovers a critical role for the lymph node microenvironment in endowing lymphatic endothelial cells with potent tolerogenic properties.


Assuntos
Microambiente Celular , Células Endoteliais/metabolismo , Endotélio Linfático/metabolismo , Tolerância Imunológica , Linfonodos/imunologia , Linfonodos/metabolismo , Animais , Animais Recém-Nascidos , Linfócitos B/imunologia , Linfócitos B/metabolismo , Antígeno B7-H1/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Moléculas de Adesão Celular/metabolismo , Microambiente Celular/imunologia , Receptor beta de Linfotoxina/metabolismo , Camundongos , Camundongos Knockout , Monofenol Mono-Oxigenase/metabolismo , Mucoproteínas , Fenótipo , Transdução de Sinais , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
9.
J Reprod Immunol ; 100(1): 66-75, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24080233

RESUMO

CD4+ CD25+ regulatory T cells (Tregs) strongly influence the early and late autoimmune responses to meiotic germ cell antigens (MGCA) and the gonadal immunopathology in vasectomized mice. This is supported by the published and recently acquired information presented here. Within 24h of unilateral vasectomy (uni-vx) the ipsilateral epididymis undergoes epithelial cell apoptosis followed by necrosis, severe inflammation, and granuloma formation. Unexpectedly, vasectomy alone induced MGCA-specific tolerance. In contrast, uni-vx plus simultaneous Treg depletion resulted in MGCA-specific autoimmune response and bilateral autoimmune orchitis. Both tolerance and autoimmunity were strictly linked to the early epididymal injury. We now discovered that testicular autoimmunity in uni-vx mice did not occur when Treg depletion was delayed by one week. Remarkably, this delayed Treg depletion also prevented tolerance induction. Therefore, tolerance depends on a rapid de novo Treg response to MGCA exposed after vasectomy. Moreover, tolerance was blunted in mice genetically deficient in PD-1 ligand, suggesting the involvement of induced Treg. We conclude that pre-existing natural Treg prevents post-vasectomy autoimmunity, whereas vasectomy-induced Treg maintains post-vasectomy tolerance. We further discovered that vasectomized mice were still resistant to autoimmune orchitis induction for at least 12-16 months; thus, tolerance is long-lasting. Although significant sperm autoantibodies of low titers became detectable in uni-vx mice at 7 months, the antibody titers fluctuated over time, suggesting a dynamic "balance" between the autoimmune and tolerance states. Finally, we observed severe epididymal fibrosis and hypo-spermatogenesis at 12 months after uni-vx: findings of highly critical clinical significance.


Assuntos
Epididimo/patologia , Orquite/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Vasectomia , Animais , Autoanticorpos/sangue , Autoimunidade/genética , Antígenos CD4/metabolismo , Fibrose/etiologia , Humanos , Tolerância Imunológica/genética , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Depleção Linfocítica , Masculino , Proteínas de Membrana/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Orquite/etiologia , Receptor de Morte Celular Programada 1/genética , Vasectomia/efeitos adversos
10.
Front Immunol ; 3: 305, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23060883

RESUMO

The lymphatic vasculature provides routes for dendritic cell and lymphocyte migration into and out of lymph nodes. Lymphatic endothelial cells (LEC) control these processes by expression of CCL21, sphingosine-1-phosphate, and adhesion molecules. LEC express MHC-I and MHC-II, but not costimulatory molecules, and present antigen on MHC-I via both direct and cross-presentation. Whether LEC present to CD4 T cells on MHC-II is unknown. Interestingly, LEC express antigens otherwise restricted to a small number of peripheral tissues in an autoimmune regulatory element-independent manner. Direct presentation of peripheral tissue antigens (PTA) to CD8 T cells results in abortive proliferation and deletion, due to both a lack of costimulation and active PD-L1 engagement. Autoimmunity develops when deletion is subverted, suggesting that LEC presentation of PTA could lead to human disease if PD-1 signaling were impaired by genetic polymorphisms, or aberrant costimulation occurred during inflammation. The expression of additional inhibitory molecules, which are not involved in LEC-mediated deletion, suggests that LEC may have additional immunoregulatory roles. LEC express receptors for several immunomodulatory molecules whose engagement alters their phenotype and function. In this review we describe the role of LEC in distinct anatomical locations in controlling immune cell trafficking, as well as their emerging role in the regulation of T cell tolerance and immunity.

11.
J Exp Med ; 207(4): 681-8, 2010 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-20308365

RESUMO

Peripheral immune tolerance is generally thought to result from cross-presentation of tissue-derived proteins by quiescent tissue-resident dendritic cells to self-reactive T cells that have escaped thymic negative selection, leading to anergy or deletion. Recently, we and others have implicated the lymph node (LN) stroma in mediating CD8 T cell peripheral tolerance. We demonstrate that LN-resident lymphatic endothelial cells express multiple peripheral tissue antigens (PTAs) independent of the autoimmune regulator (Aire). They directly present an epitope derived from one of these, the melanocyte-specific protein tyrosinase, to tyrosinase-specific CD8 T cells, leading to their deletion. We also show that other LN stromal subpopulations express distinct PTAs by mechanisms that vary in their Aire dependence. These results establish lymphatic endothelial cells, and potentially other LN-resident cells, as systemic mediators of peripheral immune tolerance.


Assuntos
Apresentação de Antígeno/imunologia , Células Endoteliais/imunologia , Tolerância Imunológica/imunologia , Linfonodos/citologia , Linfonodos/imunologia , Fatores de Transcrição/genética , Animais , Antígenos de Neoplasias/genética , Autoantígenos/genética , Autoantígenos/imunologia , Autoantígenos/metabolismo , Proliferação de Células , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Epitopos de Linfócito T/imunologia , Epitopos de Linfócito T/metabolismo , Expressão Gênica/genética , Expressão Gênica/imunologia , Glutamato Descarboxilase/genética , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Imunofenotipagem , Ativação Linfocitária/imunologia , Antígeno MART-1 , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Camundongos Transgênicos , Monofenol Mono-Oxigenase/genética , Monofenol Mono-Oxigenase/imunologia , Monofenol Mono-Oxigenase/metabolismo , Proteínas de Neoplasias/genética , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Células Estromais/citologia , Células Estromais/imunologia , Células Estromais/metabolismo , Linfócitos T/citologia , Linfócitos T/imunologia , Proteína AIRE
12.
Immunity ; 24(5): 503-6, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16713966

RESUMO

MHC class I binding peptides are generated via cytosolic degradation of a previously undefined substrate. In this issue of Immunity, pre-degradation polypeptide intermediates bound to a cytosolic chaperone is isolated.


Assuntos
Antígenos de Histocompatibilidade Classe I/imunologia , Modelos Imunológicos , Peptídeos/imunologia , Transdução de Sinais/imunologia , Animais , Apresentação de Antígeno , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Peptídeos/metabolismo
13.
Immunology ; 119(1): 63-73, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16764686

RESUMO

CD8+ T cells play a crucial role in protective immunity to viruses and tumours. Antiviral CD8+ T cells are initially activated by professional antigen presenting cells (pAPCs) that are directly infected by viruses (direct-priming) or following uptake of exogenous antigen transferred from virus-infected or tumour cells (cross-priming). In order to efficiently target each of these antigen-processing pathways during vaccine design, it is necessary to delineate the properties of the natural substrates for either of these antigen-processing pathways. In this study, we utilized a novel T-cell receptor (TCR) transgenic mouse to examine the requirement for both antigen synthesis and synthesis of other cellular factors during direct or cross-priming. We found that direct presentation required ongoing synthesis of antigen, but that cross-priming favoured long-lived antigens and did not require ongoing antigen production. Even after prolonged blockade of protein synthesis in the donor cell, cross-priming was unaffected. In contrast, direct-presentation was almost undetectable in the absence of antigen neosynthesis and required ongoing protein synthesis. This suggests that the direct- and cross-priming pathways may utilize differing pools of antigen, an observation that has far-reaching implications for the rational design of vaccines aimed at the generation of protective CD8+ T cells.


Assuntos
Apresentação de Antígeno , Células Apresentadoras de Antígenos/imunologia , Antígenos/imunologia , Linfócitos T CD8-Positivos/imunologia , Apresentação Cruzada/fisiologia , Viroses/imunologia , Transferência Adotiva/métodos , Animais , Células Apresentadoras de Antígenos/efeitos dos fármacos , Antígenos/biossíntese , Linhagem Celular , Cicloeximida/farmacologia , Eletroporação , Citometria de Fluxo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neoplasias/imunologia , Neoplasias/prevenção & controle , Inibidores da Síntese de Proteínas/farmacologia , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Viroses/prevenção & controle
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