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Doctoral Thesis
DOI
https://doi.org/10.11606/T.5.2008.tde-04082008-102804
Document
Author
Full name
Bosco Christiano Maciel da Silva
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2008
Supervisor
Committee
Vasconcelos, Dewton de Moraes (President)
Brigido, Luís Fernando de Macedo
Goto, Hiro
Pannuti, Claudio Sergio
Vilela, Maria Marluce dos Santos
Title in Portuguese
Estudo do reconhecimento de epitopos das proteínas Gag e Nef do HIV-1 por linfócitos T em indivíduos cronicamente infectados pelo HIV-1 não progressores por longo tempo
Keywords in Portuguese
Antígenos HLA
Epitopos de linfócito T
HIV
Linfócito T
Peptídeos
Síndrome de imunodeficiência adquirida
Sobreviventes de longo prazo ao HIV
Abstract in Portuguese
Os linfócitos T têm um papel central no controle da infecção pelo HIV-1. As respostas mediadas por esses linfócitos contra epitopos do HIV-1 restritos a moléculas HLA de classe I podem estar associadas à proteção natural em indivíduos LTNP. Relatos sugerem que determinados alelos HLA apresentamse mais representados entre os LTNP. Para avaliar esses aspectos na coorte francesa ALT, coletamos células mononucleares de sangue periférico (CMSP) de 24 indivíduos LTNP e verificamos a freqüência de respostas específicas para o HIV-1. Para isso, utilizamos pools de peptídeos sobrepostos de Gag e regiões imunodominantes da RT e Nef, e identificamos epitopos do HIV-1 restritos a moléculas HLA de classe I, associados ou não à proteção, através do ensaio de ELISPOT IFN-?. Todos os indivíduos apresentaram respostas específicas aos pools testados, com uma mediana de 5 (2-12). Todas as proteínas do HIV-1 foram reconhecidas, sendo que Gag-p24 e Nef foram as mais freqüentemente reconhecidas pelas CMSP dos indivíduos avaliados. A intensidade total de resposta de linfócitos T específicos aos pools de Gag, RT e Nef do HIV-1 em cada indivíduo variou de 160 a 12307 SFC/106 CMSP (mediana: 2025). Observamos o reconhecimento de 22 epitopos já descritos na literatura, contidos nas proteínas Gag-p17, Gag-p24 e Nef do HIV-1, restritos a moléculas HLA de classe I, a maioria descrita como protetoras da progressão para a doença. Quatro novos epitopos ainda não descritos na literatura também foram observados. Concluímos que: respostas específicas mediadas por linfócitos T, eficazes e dirigidas contra um amplo painel de epitopos do HIV-1, estão presentes nos indivíduos LTNP; a presença de moléculas HLA de classe I associadas à proteção favorece o reconhecimento preferencial de epitopos do HIV-1 restritos por elas na maioria dos indivíduos LTNP; esses aspectos devem ser levados em conta na perspectiva do desenvolvimento de uma vacina candidata contra o HIV-1.
Title in English
Study of the recognition of HIV-1 Gag and Nef epitopes by T lymphocytes in chronically infected HIV-1 Long-Term Non-Progressors
Keywords in English
Acquired immunodeficiency syndrome
Epitopes T lymphocyte
HIV
HIV long-term survivors
HLA antigens
Peptides
T lymphocytes
Abstract in English
T lymphocytes (T-L) have a paramount role in the control of HIV-1 infection. The responses mediated by these cells against HLA class I epitopes may be associated to the natural protection in long-term non-progressors (LTNP). The literature suggests that some HLA alleles relate to the protection against the immune dysfunction. The aim of this research is to study the recognition of HIV-1 Gag, Nef and RT epitopes by T-L through an ELISPOT IFN-? assay in the peripheral blood mononuclear cells (PBMC) of 24 LTNP selected from French ALT study group. We evaluated the frequency of anti-HIV-1 responses and identified HLA class I epitopes. All individuals presented specific responses to the pools of peptides tested with a median of 5 (2-12). Gag-p24 and Nef were the most frequently recognized proteins. The magnitude of the responses varied from 160 to 12307 SFC/106 PBMC (median=2025). We observed the recognition of 22 epitopes already described in HIV-1 Gag-p17, Gag-p24 and Nef, restricted to HLA class I molecules reported as protective. We have also observed four new epitopes not already described in the literature. Our results suggest that: HIV-1 responses by T-L are present in LTNP; the presence of HLA class I molecules associated with protection in the majority of LTNP are related to the recognition of MHC restricted HIV-1 epitopes; these aspects must be taken into account in the development of a candidate vaccine against HIV-1.
 
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BoscoCMdaSilva.pdf (8.18 Mbytes)
Publishing Date
2008-08-06
 
WARNING: The material described below relates to works resulting from this thesis or dissertation. The contents of these works are the author's responsibility.
  • XIE, Jing, et al. Distinct differentiation profiles of HIV-Gag and Nef-specific central memory CD8+ T cells associated with HLA-B57/5801 and virus control [doi:10.1097/QAD.0b013e32833e5009]. AIDS [online], 2010, p. 1-2329.
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