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[PMID]:29381830
[Au] Autor:Sioud M
[Ad] Endereço:Department of Cancer Immunology, Oslo University Hospital, The Norwegian Radium Hospital, Montebello, Oslo, Norway.
[Ti] Título:T-cell cross-reactivity may explain the large variation in how cancer patients respond to checkpoint inhibitors.
[So] Source:Scand J Immunol;87(3), 2018 Mar.
[Is] ISSN:1365-3083
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The therapeutic use of the immune system to specifically attack tumours has been a long-standing vision among tumour immunologists. Recently, the use of checkpoint inhibitors to turn-off immunosuppressive signals has proven to be effective in enhancing T-cell reactivity against patient-specific neoantigens, resulting from somatic mutations. Several of the identified T-cell epitopes share similarity with common bacterial and viral antigens, suggesting the involvement of pre-existing microbial cross-reactive T cells in rapid and durable tumour regression seen in some patients. This notion of T-cell cross-reactivity is further supported by the findings that intestinal bacteria can influence checkpoint-blockade therapy. Moreover, early data indicate the presence of such T cells in long-term survival breast cancer patients. This review highlights the main challenges for cancer immunotherapy and discusses the potential contribution of T-cell cross-reactivity in cancer immunotherapy and whether it can be used as a biomarker to predict the responsiveness to checkpoint inhibitors.
[Mh] Termos MeSH primário: Reações Cruzadas/imunologia
Imunoterapia/métodos
Neoplasias/imunologia
Neoplasias/terapia
Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Antígenos de Bactérias/imunologia
Antígenos de Neoplasias/imunologia
Antígenos Virais/imunologia
Biomarcadores Tumorais/imunologia
Antígeno CTLA-4/antagonistas & inibidores
Células Dendríticas/imunologia
Epitopos de Linfócito T/imunologia
Seres Humanos
Ativação Linfocitária/imunologia
Receptor de Morte Celular Programada 1/antagonistas & inibidores
Receptores Imunológicos/antagonistas & inibidores
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antigens, Bacterial); 0 (Antigens, Neoplasm); 0 (Antigens, Viral); 0 (Biomarkers, Tumor); 0 (CTLA-4 Antigen); 0 (Epitopes, T-Lymphocyte); 0 (PDCD1 protein, human); 0 (Programmed Cell Death 1 Receptor); 0 (Receptors, Immunologic); 0 (TIGIT protein, human)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180131
[St] Status:MEDLINE
[do] DOI:10.1111/sji.12643


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[PMID]:28459074
[Au] Autor:Rosenthal KS; Stone S; Koski G; Zimmerman DH
[Ad] Endereço:College of Medicine, Roseman University of Health Sciences, 10530 Discovery Drive, Las Vegas, NV 89135, USA.
[Ti] Título:LEAPS Vaccine Incorporating HER-2/neu Epitope Elicits Protection That Prevents and Limits Tumor Growth and Spread of Breast Cancer in a Mouse Model.
[So] Source:J Immunol Res;2017:3613505, 2017.
[Is] ISSN:2314-7156
[Cp] País de publicação:Egypt
[La] Idioma:eng
[Ab] Resumo:The prototype J-LEAPS T cell vaccine for HER-2/neu breast cancer (J-HER) consists of the murine HER-2/neu H-2 CD8 T cell epitope covalently attached through a triglycine linker to the J-immune cell binding ligand (ICBL) (human 2 microglobulin peptide). The J-ICBL was chosen for its potential to promote Th1/Tc1 responses. In this proof-of-concept study, the ability of J-HER to prevent or treat cancer was tested in the TUBO cell-challenged BALB/c mouse model for HER-2/neu-expressing tumors. The J-HER vaccine was administered as an emulsion in Montanide ISA-51 without the need for a more potent adjuvant. When administered as a prophylactic vaccination before tumor challenge, J-HER protected against tumor development for at least 48 days. Despite eliciting protection, antibody production in J-HER-immunized, TUBO-challenged mice was less than that in unimmunized mice. More importantly, therapeutic administration of J-HER one week after challenge with TUBO breast cancer cells limited the spread of the tumors and the morbidity and the mortality in the challenged mice. The ability to elicit responses that prevent spread of the TUBO tumor by J-HER suggests its utility as a neoimmunoadjuvant therapy to surgery. Individual or mixtures of J-LEAPS vaccines can be readily prepared to include different CD8 T cell epitopes to optimize tumor therapy and customize treatment for individuals with different HLA types.
[Mh] Termos MeSH primário: Vacinas Anticâncer
Neoplasias Mamárias Experimentais/prevenção & controle
Neoplasias Mamárias Experimentais/terapia
[Mh] Termos MeSH secundário: Animais
Neoplasias da Mama/genética
Neoplasias da Mama/imunologia
Neoplasias da Mama/prevenção & controle
Neoplasias da Mama/terapia
Linfócitos T CD8-Positivos/imunologia
Vacinas Anticâncer/genética
Vacinas Anticâncer/imunologia
Vacinas Anticâncer/uso terapêutico
Linhagem Celular Tumoral
Modelos Animais de Doenças
Progressão da Doença
Epitopos de Linfócito T/imunologia
Feminino
Genes erbB-2
Imunoglobulina G/sangue
Neoplasias Mamárias Experimentais/imunologia
Neoplasias Mamárias Experimentais/patologia
Camundongos
Camundongos Endogâmicos BALB C
Metástase Neoplásica/prevenção & controle
Estudo de Prova de Conceito
Linfócitos T Citotóxicos/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cancer Vaccines); 0 (Epitopes, T-Lymphocyte); 0 (Immunoglobulin G)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180208
[Lr] Data última revisão:
180208
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE
[do] DOI:10.1155/2017/3613505


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[PMID]:27777777
[Au] Autor:Weir GM; Hrytsenko O; Quinton T; Berinstein NL; Stanford MM; Mansour M
[Ad] Endereço:Immunovaccine Inc., 1344 Summer St., Halifax, NS B3H 0A8 Canada.
[Ti] Título:Anti-PD-1 increases the clonality and activity of tumor infiltrating antigen specific T cells induced by a potent immune therapy consisting of vaccine and metronomic cyclophosphamide.
[So] Source:J Immunother Cancer;4:68, 2016.
[Is] ISSN:2051-1426
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Future cancer immunotherapies will combine multiple treatments to generate functional immune responses to cancer antigens through synergistic, multi-modal mechanisms. In this study we explored the combination of three distinct immunotherapies: a class I restricted peptide-based cancer vaccine, metronomic cyclophosphamide (mCPA) and anti-PD-1 treatment in a murine tumor model expressing HPV16 E7 (C3). METHODS: Mice were implanted with C3 tumors subcutaneously. Tumor bearing mice were treated with mCPA (20 mg/kg/day PO) for seven continuous days on alternating weeks, vaccinated with HPV16 E7 peptide antigen formulated in the DepoVax (DPX) adjuvanting platform every second week, and administered anti-PD-1 (200 µg/dose IP) after each vaccination. Efficacy was measured by following tumor growth and survival. Immunogenicity was measured by IFN-γ ELISpot of spleen, vaccine draining lymph nodes and tumor draining lymph nodes. Tumor infiltration was measured by flow cytometry for CD8α peptide-specific T cells and RT-qPCR for cytotoxic proteins. The clonality of tumor infiltrating T cells was measured by TCRß sequencing using genomic DNA. RESULTS: Untreated C3 tumors had low expression of PD-L1 in vivo and anti-PD-1 therapy alone provided no protection from tumor growth. Treatment with DPX/mCPA could delay tumor growth, and tri-therapy with DPX/mCPA/anti-PD-1 provided long-term control of tumors. We found that treatment with DPX/mCPA/anti-PD-1 enhanced systemic antigen-specific immune responses detected in the spleen as determined by IFN-γ ELISpot compared to those in the DPX/mCPA group, but immune responses in tumor-draining lymph nodes were not increased. Although no increases in antigen-specific CD8α TILs could be detected, there was a trend for increased expression of cytotoxic genes within the tumor microenvironment as well as an increase in clonality in mice treated with DPX/mCPA/anti-PD-1 compared to those with anti-PD-1 alone or DPX/mCPA. Using a library of antigen-specific CD8α T cell clones, we found that antigen-specific clones were more frequently expanded in the DPX/mCPA/anti-PD-1 treated group. CONCLUSIONS: These results demonstrate how the efficacy of anti-PD-1 may be improved by combination with a potent and targeted T cell activating immune therapy.
[Mh] Termos MeSH primário: Antineoplásicos Imunológicos/farmacologia
Vacinas Anticâncer/imunologia
Ciclofosfamida/administração & dosagem
Linfócitos do Interstício Tumoral/efeitos dos fármacos
Linfócitos do Interstício Tumoral/imunologia
Neoplasias/imunologia
Receptor de Morte Celular Programada 1/antagonistas & inibidores
Subpopulações de Linfócitos T/efeitos dos fármacos
Subpopulações de Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Administração Metronômica
Animais
Antineoplásicos Imunológicos/uso terapêutico
Antígeno B7-H1/genética
Antígeno B7-H1/metabolismo
Linfócitos T CD8-Positivos/efeitos dos fármacos
Linfócitos T CD8-Positivos/imunologia
Linfócitos T CD8-Positivos/metabolismo
Linhagem Celular Tumoral
Evolução Clonal/efeitos dos fármacos
Evolução Clonal/imunologia
Citotoxicidade Imunológica
Modelos Animais de Doenças
Epitopos de Linfócito T/química
Epitopos de Linfócito T/imunologia
Feminino
Expressão Gênica
Seres Humanos
Imunomodulação/efeitos dos fármacos
Linfócitos do Interstício Tumoral/metabolismo
Camundongos
Neoplasias/metabolismo
Neoplasias/patologia
Neoplasias/terapia
Receptor de Morte Celular Programada 1/genética
Receptor de Morte Celular Programada 1/metabolismo
Especificidade do Receptor de Antígeno de Linfócitos T/efeitos dos fármacos
Especificidade do Receptor de Antígeno de Linfócitos T/imunologia
Subpopulações de Linfócitos T/metabolismo
Microambiente Tumoral/efeitos dos fármacos
Microambiente Tumoral/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents, Immunological); 0 (B7-H1 Antigen); 0 (Cancer Vaccines); 0 (Epitopes, T-Lymphocyte); 0 (Programmed Cell Death 1 Receptor); 8N3DW7272P (Cyclophosphamide)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180201
[Lr] Data última revisão:
180201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE


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[PMID]:28448594
[Au] Autor:Borthwick N; Lin Z; Akahoshi T; Llano A; Silva-Arrieta S; Ahmed T; Dorrell L; Brander C; Murakoshi H; Takiguchi M; Hanke T
[Ad] Endereço:The Jenner Institute, University of Oxford, Oxford, United Kingdom.
[Ti] Título:Novel, in-natural-infection subdominant HIV-1 CD8+ T-cell epitopes revealed in human recipients of conserved-region T-cell vaccines.
[So] Source:PLoS One;12(4):e0176418, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Fine definition of targeted CD8+ T-cell epitopes and their human leucocyte antigen (HLA) class I restriction informs iterative improvements of HIV-1 T-cell vaccine designs and may predict early vaccine success or failure. Here, lymphocytes from volunteers, who had received candidate HIVconsv vaccines expressing conserved sub-protein regions of HIV-1, were used to define the optimum-length target epitopes and their HLA restriction. In HIV-1-positive patients, CD8+ T-cell responses predominantly recognize immunodominant, but hypervariable and therefore less protective epitopes. The less variable, more protective epitopes in conserved regions are typically subdominant. Therefore, induction of strong responses to conserved regions by vaccination provides an opportunity to discover novel important epitopes. METHODS: Cryopreserved lymphocytes from vaccine recipients were expanded by stimulation with 15-mer responder peptides for 10 days to establish short term-cell-line (STCL) effector cells. These were subjected to intracellular cytokine staining using serially truncated peptides and peptide-pulsed 721.221 cells expressing individual HLA class I alleles to define minimal epitope length and HLA restriction by stimulation of IFN-γ and TNF-α production and surface expression of CD107a. RESULTS: Using lymphocyte samples of 12 vaccine recipients, we defined 14 previously unreported optimal CD8+ T-cell HIV-1 epitopes and their four-digit HLA allele restriction (6 HLA-A, 7 HLA-B and 1 HLA-C alleles). Further 13 novel targets with incomplete information were revealed. CONCLUSIONS: The high rate of discovery of novel CD8+ T-cell effector epitopes warrants further epitope mining in recipients of the conserved-region vaccines in other populations and informs development of HIV-1/AIDS vaccines. TRIAL REGISTRATION: ClinicalTrials.gov NCT01151319.
[Mh] Termos MeSH primário: Vacinas contra a AIDS/imunologia
Linfócitos T CD8-Positivos/imunologia
Sequência Conservada
Infecções por HIV/prevenção & controle
HIV-1/imunologia
HIV-1/fisiologia
[Mh] Termos MeSH secundário: Vacinas contra a AIDS/química
Alelos
Sequência de Aminoácidos
Epitopos de Linfócito T/química
Epitopos de Linfócito T/imunologia
Infecções por HIV/genética
Antígenos HLA/genética
Seres Humanos
[Pt] Tipo de publicação:CLINICAL TRIAL; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AIDS Vaccines); 0 (Epitopes, T-Lymphocyte); 0 (HLA Antigens)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180125
[Lr] Data última revisão:
180125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170428
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0176418


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[PMID]:28741316
[Au] Autor:Hogg A; Sui Y; Ben-Sasson SZ; Paul WE; Berzofsky JA
[Ad] Endereço:Vaccine Branch, Center for Cancer Research, National Cancer Institute.
[Ti] Título:Role of CD4 T cell helper subsets in immune response and deviation of CD8 T cells in mice.
[So] Source:Eur J Immunol;47(12):2059-2069, 2017 Dec.
[Is] ISSN:1521-4141
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:The ability of different CD4 T cell subsets to help CD8 T-cell response is not fully understood. Here, we found using the murine system that Th17 cells induced by IL-1ß, unlike Th1, were not effective helpers for antiviral CD8 responses as measured by IFNγ-producing cells or protection against virus infection. However, they skewed CD8 responses to a Tc17 phenotype. Thus, the apparent lack of help was actually immune deviation. This skewing depended on both IL-21 and IL-23. To overcome this effect, we inhibited Th17 induction by blocking TGF-ß. Anti-TGF-ß allowed the IL-1ß adjuvant to enhance CD8 T-cell responses without skewing the phenotype to Tc17, thereby providing an approach to harness the benefit of common IL-1-inducing adjuvants like alum without immune deviation.
[Mh] Termos MeSH primário: Linfócitos T CD4-Positivos/imunologia
Linfócitos T CD8-Positivos/imunologia
Imunidade Celular/imunologia
Linfócitos T Auxiliares-Indutores/imunologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Bloqueadores/imunologia
Anticorpos Bloqueadores/farmacologia
Linfócitos T CD4-Positivos/metabolismo
Linfócitos T CD8-Positivos/metabolismo
Epitopos de Linfócito T/imunologia
Citometria de Fluxo
Interferon gama/imunologia
Interferon gama/metabolismo
Interleucina-1beta/imunologia
Interleucina-1beta/metabolismo
Interleucina-1beta/farmacologia
Camundongos Endogâmicos BALB C
Camundongos Endogâmicos C57BL
Linfócitos T Auxiliares-Indutores/metabolismo
Células Th1/imunologia
Células Th1/metabolismo
Células Th17/efeitos dos fármacos
Células Th17/imunologia
Células Th17/metabolismo
Fator de Crescimento Transformador beta/imunologia
Fator de Crescimento Transformador beta/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Blocking); 0 (Epitopes, T-Lymphocyte); 0 (Interleukin-1beta); 0 (Transforming Growth Factor beta); 82115-62-6 (Interferon-gamma)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171218
[Lr] Data última revisão:
171218
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170726
[St] Status:MEDLINE
[do] DOI:10.1002/eji.201747091


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[PMID]:28978689
[Au] Autor:Jurtz V; Paul S; Andreatta M; Marcatili P; Peters B; Nielsen M
[Ad] Endereço:Department of Bio and Health Informatics, Technical University of Denmark, DK-2800 Lyngby, Denmark.
[Ti] Título:NetMHCpan-4.0: Improved Peptide-MHC Class I Interaction Predictions Integrating Eluted Ligand and Peptide Binding Affinity Data.
[So] Source:J Immunol;199(9):3360-3368, 2017 Nov 01.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cytotoxic T cells are of central importance in the immune system's response to disease. They recognize defective cells by binding to peptides presented on the cell surface by MHC class I molecules. Peptide binding to MHC molecules is the single most selective step in the Ag-presentation pathway. Therefore, in the quest for T cell epitopes, the prediction of peptide binding to MHC molecules has attracted widespread attention. In the past, predictors of peptide-MHC interactions have primarily been trained on binding affinity data. Recently, an increasing number of MHC-presented peptides identified by mass spectrometry have been reported containing information about peptide-processing steps in the presentation pathway and the length distribution of naturally presented peptides. In this article, we present NetMHCpan-4.0, a method trained on binding affinity and eluted ligand data leveraging the information from both data types. Large-scale benchmarking of the method demonstrates an increase in predictive performance compared with state-of-the-art methods when it comes to identification of naturally processed ligands, cancer neoantigens, and T cell epitopes.
[Mh] Termos MeSH primário: Bases de Dados de Proteínas
Epitopos de Linfócito T/imunologia
Antígenos de Histocompatibilidade Classe I/imunologia
Peptídeos/imunologia
Software
[Mh] Termos MeSH secundário: Seres Humanos
Valor Preditivo dos Testes
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Epitopes, T-Lymphocyte); 0 (Histocompatibility Antigens Class I); 0 (Peptides)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171111
[Lr] Data última revisão:
171111
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171006
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1700893


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[PMID]:28972094
[Au] Autor:Abana CO; Pilkinton MA; Gaudieri S; Chopra A; McDonnell WJ; Wanjalla C; Barnett L; Gangula R; Hager C; Jung DK; Engelhardt BG; Jagasia MH; Klenerman P; Phillips EJ; Koelle DM; Kalams SA; Mallal SA
[Ad] Endereço:Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232.
[Ti] Título:Cytomegalovirus (CMV) Epitope-Specific CD4 T Cells Are Inflated in HIV CMV Subjects.
[So] Source:J Immunol;199(9):3187-3201, 2017 Nov 01.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Select CMV epitopes drive life-long CD8 T cell memory inflation, but the extent of CD4 memory inflation is poorly studied. CD4 T cells specific for human CMV (HCMV) are elevated in HIV HCMV subjects. To determine whether HCMV epitope-specific CD4 T cell memory inflation occurs during HIV infection, we used HLA-DR7 (DRB1*07:01) tetramers loaded with the glycoprotein B DYSNTHSTRYV (DYS) epitope to characterize circulating CD4 T cells in coinfected HLA-DR7 long-term nonprogressor HIV subjects with undetectable HCMV plasma viremia. DYS-specific CD4 T cells were inflated among these HIV subjects compared with those from an HIV HCMV HLA-DR7 cohort or with HLA-DR7-restricted CD4 T cells from the HIV-coinfected cohort that were specific for epitopes of HCMV phosphoprotein-65, tetanus toxoid precursor, EBV nuclear Ag 2, or HIV gag protein. Inflated DYS-specific CD4 T cells consisted of effector memory or effector memory-RA subsets with restricted TCRß usage and nearly monoclonal CDR3 containing novel conserved amino acids. Expression of this near-monoclonal TCR in a Jurkat cell-transfection system validated fine DYS specificity. Inflated cells were polyfunctional, not senescent, and displayed high ex vivo levels of granzyme B, CX CR1, CD38, or HLA-DR but less often coexpressed CD38 and HLA-DR The inflation mechanism did not involve apoptosis suppression, increased proliferation, or HIV gag cross-reactivity. Instead, the findings suggest that intermittent or chronic expression of epitopes, such as DYS, drive inflation of activated CD4 T cells that home to endothelial cells and have the potential to mediate cytotoxicity and vascular disease.
[Mh] Termos MeSH primário: Linfócitos T CD4-Positivos/imunologia
Infecções por Citomegalovirus/imunologia
Citomegalovirus/imunologia
Epitopos de Linfócito T/imunologia
Infecções por HIV/imunologia
HIV-1/imunologia
Proteínas Virais/imunologia
[Mh] Termos MeSH secundário: ADP-Ribosil Ciclase 1/imunologia
Linfócitos T CD4-Positivos/patologia
Infecções por Citomegalovirus/patologia
Feminino
Infecções por HIV/patologia
Antígeno HLA-DR7/imunologia
Seres Humanos
Memória Imunológica
Masculino
Glicoproteínas de Membrana/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Epitopes, T-Lymphocyte); 0 (HLA-DR7 Antigen); 0 (Membrane Glycoproteins); 0 (Viral Proteins); EC 3.2.2.5 (CD38 protein, human); EC 3.2.2.6 (ADP-ribosyl Cyclase 1)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171004
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1700851


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[PMID]:28945243
[Au] Autor:Culshaw A; Ladell K; Gras S; McLaren JE; Miners KL; Farenc C; van den Heuvel H; Gostick E; Dejnirattisai W; Wangteeraprasert A; Duangchinda T; Chotiyarnwong P; Limpitikul W; Vasanawathana S; Malasit P; Dong T; Rossjohn J; Mongkolsapaya J; Price DA; Screaton GR
[Ad] Endereço:Department of Medicine, Imperial College London, London, UK.
[Ti] Título:Germline bias dictates cross-serotype reactivity in a common dengue-virus-specific CD8 T cell response.
[So] Source:Nat Immunol;18(11):1228-1237, 2017 Nov.
[Is] ISSN:1529-2916
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Adaptive immune responses protect against infection with dengue virus (DENV), yet cross-reactivity with distinct serotypes can precipitate life-threatening clinical disease. We found that clonotypes expressing the T cell antigen receptor (TCR) ß-chain variable region 11 (TRBV11-2) were 'preferentially' activated and mobilized within immunodominant human-leukocyte-antigen-(HLA)-A*11:01-restricted CD8 T cell populations specific for variants of the nonstructural protein epitope NS3 that characterize the serotypes DENV1, DENV3 and DENV4. In contrast, the NS3 -DENV2-specific repertoire was largely devoid of such TCRs. Structural analysis of a representative TRBV11-2 TCR demonstrated that cross-serotype reactivity was governed by unique interplay between the variable antigenic determinant and germline-encoded residues in the second ß-chain complementarity-determining region (CDR2ß). Extensive mutagenesis studies of three distinct TRBV11-2 TCRs further confirmed that antigen recognition was dependent on key contacts between the serotype-defined peptide and discrete residues in the CDR2ß loop. Collectively, these data reveal an innate-like mode of epitope recognition with potential implications for the outcome of sequential exposure to heterologous DENVs.
[Mh] Termos MeSH primário: Linfócitos T CD8-Positivos/imunologia
Reações Cruzadas/imunologia
Vírus da Dengue/imunologia
Mutação em Linhagem Germinativa/imunologia
Receptores de Antígenos de Linfócitos T alfa-beta/imunologia
[Mh] Termos MeSH secundário: Imunidade Adaptativa/genética
Imunidade Adaptativa/imunologia
Sequência de Aminoácidos
Linfócitos T CD8-Positivos/metabolismo
Linfócitos T CD8-Positivos/virologia
Regiões Determinantes de Complementaridade/genética
Regiões Determinantes de Complementaridade/imunologia
Dengue/genética
Dengue/imunologia
Dengue/virologia
Vírus da Dengue/classificação
Vírus da Dengue/genética
Epitopos de Linfócito T/química
Epitopos de Linfócito T/genética
Epitopos de Linfócito T/imunologia
Antígenos HLA-A/química
Antígenos HLA-A/genética
Antígenos HLA-A/imunologia
Seres Humanos
Modelos Moleculares
Estrutura Terciária de Proteína
Receptores de Antígenos de Linfócitos T alfa-beta/química
Receptores de Antígenos de Linfócitos T alfa-beta/genética
Serina Endopeptidases/genética
Serina Endopeptidases/imunologia
Sorotipagem
Ressonância de Plasmônio de Superfície
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Complementarity Determining Regions); 0 (Epitopes, T-Lymphocyte); 0 (HLA-A Antigens); 0 (Receptors, Antigen, T-Cell, alpha-beta); EC 3.4.21.- (NS3 protease, dengue virus); EC 3.4.21.- (Serine Endopeptidases)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170926
[St] Status:MEDLINE
[do] DOI:10.1038/ni.3850


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[PMID]:28938005
[Au] Autor:Holanda RA; Muñoz JE; Dias LS; Silva LBR; Santos JRA; Pagliari S; Vieira ÉLM; Paixão TA; Taborda CP; Santos DA; Bruña-Romero O
[Ad] Endereço:Departamento de Microbiologia, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
[Ti] Título:Recombinant vaccines of a CD4+ T-cell epitope promote efficient control of Paracoccidioides brasiliensis burden by restraining primary organ infection.
[So] Source:PLoS Negl Trop Dis;11(9):e0005927, 2017 Sep.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Paracoccidioidomycosis (PCM) is an infectious disease endemic to South America, caused by the thermally dimorphic fungi Paracoccidioides. Currently, there is no effective human vaccine that can be used in prophylactic or therapeutic regimes. We tested the hypothesis that the immunogenicity of the immunodominant CD4+ T-cell epitope (P10) of Paracoccidioides brasiliensis gp43 antigen might be significantly enhanced by using a hepatitis B virus-derived particle (VLP) as an antigen carrier. This chimera was administered to mice as a (His)6-purified protein (rPbT) or a replication-deficient human type 5 adenoviral vector (rAdPbT) in an immunoprophylaxis assay. The highly virulent Pb18 yeast strain was used to challenge our vaccine candidates. Fungal challenge evoked robust P10-specific memory CD4+ T cells secreting protective Th-1 cytokines in most groups of immunized mice. Furthermore, the highest level of fungal burden control was achieved when rAdPbT was inoculated in a homologous prime-boost regimen, with 10-fold less CFU recovering than in non-vaccinated mice. Systemic Pb18 spreading was only prevented when rAdPbT was previously inoculated. In summary, we present here VLP/P10 formulations as vaccine candidates against PCM, some of which have demonstrated for the first time their ability to prevent progression of this pernicious fungal disease, which represents a significant social burden in developing countries.
[Mh] Termos MeSH primário: Antígenos de Fungos/imunologia
Linfócitos T CD4-Positivos/imunologia
Epitopos de Linfócito T/imunologia
Proteínas Fúngicas/imunologia
Vacinas Fúngicas/administração & dosagem
Glicoproteínas/imunologia
Paracoccidioides/crescimento & desenvolvimento
Paracoccidioides/imunologia
Paracoccidioidomicose/prevenção & controle
[Mh] Termos MeSH secundário: Animais
Citocinas/imunologia
Citocinas/secreção
Epitopos de Linfócito T/genética
Vacinas Fúngicas/imunologia
Vírus da Hepatite B/genética
Imunização
Epitopos Imunodominantes/imunologia
Imunogenicidade da Vacina
Memória Imunológica
Fígado/microbiologia
Pulmão/microbiologia
Camundongos Endogâmicos BALB C
Paracoccidioidomicose/imunologia
Paracoccidioidomicose/microbiologia
Baço/microbiologia
Células Th1/imunologia
Vacinas Sintéticas/administração & dosagem
Vacinas Sintéticas/genética
Vacinas Sintéticas/imunologia
Vacinas de Partículas Semelhantes a Vírus/administração & dosagem
Vacinas de Partículas Semelhantes a Vírus/genética
Vacinas de Partículas Semelhantes a Vírus/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (43 kDa protein, Paracoccidioides); 0 (Antigens, Fungal); 0 (Cytokines); 0 (Epitopes, T-Lymphocyte); 0 (Fungal Proteins); 0 (Fungal Vaccines); 0 (Glycoproteins); 0 (Immunodominant Epitopes); 0 (Vaccines, Synthetic); 0 (Vaccines, Virus-Like Particle)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171025
[Lr] Data última revisão:
171025
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170923
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005927


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[PMID]:28934310
[Au] Autor:Tumiotto C; Riviere L; Bellecave P; Recordon-Pinson P; Vilain-Parce A; Guidicelli GL; Fleury H; Provir/Latitude 45 collaborating group
[Ad] Endereço:Laboratoire de Virologie, CHU de Bordeaux et CNRS UMR 5234, Bordeaux, France.
[Ti] Título:Sanger and Next-Generation Sequencing data for characterization of CTL epitopes in archived HIV-1 proviral DNA.
[So] Source:PLoS One;12(9):e0185211, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:One of the strategies for curing viral HIV-1 is a therapeutic vaccine involving the stimulation of cytotoxic CD8-positive T cells (CTL) that are Human Leucocyte Antigen (HLA)-restricted. The lack of efficiency of previous vaccination strategies may have been due to the immunogenic peptides used, which could be different from a patient's virus epitopes and lead to a poor CTL response. To counteract this lack of specificity, conserved epitopes must be targeted. One alternative is to gather as many data as possible from a large number of patients on their HIV-1 proviral archived epitope variants, taking into account their genetic background to select the best presented CTL epitopes. In order to process big data generated by Next-Generation Sequencing (NGS) of the DNA of HIV-infected patients, we have developed a software package called TutuGenetics. This tool combines an alignment derived either from Sanger or NGS files, HLA typing, target gene and a CTL epitope list as input files. It allows automatic translation after correction of the alignment obtained between the HxB2 reference and the reads, followed by automatic calculation of the MHC IC50 value for each epitope variant and the HLA allele of the patient by using NetMHCpan 3.0, resulting in a csv file as output result. We validated this new tool by comparing Sanger and NGS (454, Roche) sequences obtained from the proviral DNA of patients at success of ART included in the Provir Latitude 45 study and showed a 90% correlation between the quantitative results of NGS and Sanger. This automated analysis combined with complementary samples should yield more data regarding the archived CTL epitopes according to the patients' HLA alleles and will be useful for screening epitopes that in theory are presented efficiently to the HLA groove, thus constituting promising immunogenic peptides for a therapeutic vaccine.
[Mh] Termos MeSH primário: Linfócitos T CD8-Positivos/imunologia
DNA Viral/genética
Epitopos de Linfócito T/imunologia
HIV-1/genética
HIV-1/imunologia
Sequenciamento de Nucleotídeos em Larga Escala
Análise de Sequência de DNA
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Epitopos de Linfócito T/química
Seres Humanos
Software
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Viral); 0 (Epitopes, T-Lymphocyte)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171018
[Lr] Data última revisão:
171018
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170922
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0185211



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