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2030-01-01
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- IOC - Artigos de Periódicos [12491]
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BROAD REPERTOIRE OF THE CD4+ TH CELL RESPONSE IN SPONTANEOUSLY CONTROLLED HEPATITIS C VIRUS INFECTION INCLUDES DOMINANT AND HIGHLY PROMISCUOUS EPITOPES
Infecção
Resposta celular CD4 Th
Epitopos Dominantes e Altamente Promíscuos
Author
Affilliation
Partners AIDS Research Center. Infectious Disease Division. Gastrointestinal Unit. Massachusetts General Hospital. Boston, MA, USA / Howard Hughes Medical Institute. Boston, MA, USA.
Partners AIDS Research Center and Infectious Disease Division. Harvard Medical School, Boston, MA. USA;
Partners AIDS Research Center and Infectious Disease Division. Harvard Medical School, Boston, MA, USA.
Partners AIDS Research Center and Infectious Disease Division. Harvard Medical School, Boston, MA, USA.
Partners AIDS Research Center and Infectious Disease Division. Harvard Medical School, Boston, MA., USA.
Partners AIDS Research Center and Infectious Disease Division. Harvard Medical School, Boston, MA, USA
Partners AIDS Research Center and Infectious Disease Division. Harvard Medical School, Boston, MA, USA. / Lemuel Shattuck Hospital. Jamaica Plain, MA, USA.
Partners AIDS Research Center and Infectious Disease Division. Harvard Medical School, Boston, MA, USA.
Partners AIDS Research Center and Infectious Disease Division. Harvard Medical School, Boston, MA, USA.
Department of Biological Sciences. California State University, San Marco, CA, USA.
Partners AIDS Research Center and Infectious Disease Division. Harvard Medical School, Boston, MA, USA.
Lemuel Shattuck Hospital. Jamaica Plain, MA, USA..
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Virologia. Rio de Janeiro, RJ. Brasil.
La Jolla Institute for Allergy and Immunology. La Jolla, CA, USA.
La Jolla Institute for Allergy and Immunology. La Jolla, CA, USA.
Gastrointestinal Unit. Massachusetts General Hospital. Boston, MA, USA.
Partners AIDS Research Center. Infectious Disease Division. Gastrointestinal Unit. Massachusetts General Hospital. Boston, MA, USA / Howard Hughes Medical Institute. Boston, MA, USA.
Partners AIDS Research Center and Infectious Disease Division. Harvard Medical School, Boston, MA. USA;
Partners AIDS Research Center and Infectious Disease Division. Harvard Medical School, Boston, MA, USA.
Partners AIDS Research Center and Infectious Disease Division. Harvard Medical School, Boston, MA, USA.
Partners AIDS Research Center and Infectious Disease Division. Harvard Medical School, Boston, MA., USA.
Partners AIDS Research Center and Infectious Disease Division. Harvard Medical School, Boston, MA, USA
Partners AIDS Research Center and Infectious Disease Division. Harvard Medical School, Boston, MA, USA. / Lemuel Shattuck Hospital. Jamaica Plain, MA, USA.
Partners AIDS Research Center and Infectious Disease Division. Harvard Medical School, Boston, MA, USA.
Partners AIDS Research Center and Infectious Disease Division. Harvard Medical School, Boston, MA, USA.
Department of Biological Sciences. California State University, San Marco, CA, USA.
Partners AIDS Research Center and Infectious Disease Division. Harvard Medical School, Boston, MA, USA.
Lemuel Shattuck Hospital. Jamaica Plain, MA, USA..
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Virologia. Rio de Janeiro, RJ. Brasil.
La Jolla Institute for Allergy and Immunology. La Jolla, CA, USA.
La Jolla Institute for Allergy and Immunology. La Jolla, CA, USA.
Gastrointestinal Unit. Massachusetts General Hospital. Boston, MA, USA.
Partners AIDS Research Center. Infectious Disease Division. Gastrointestinal Unit. Massachusetts General Hospital. Boston, MA, USA / Howard Hughes Medical Institute. Boston, MA, USA.
Abstract
A vigorous hepatitis C virus (HCV)-specific Th cell response is regarded as essential to the immunological control of HCV viremia. The aim of this study was to comprehensively define the breadth and specificity of dominant HCV-specific CD4(+) T cell epitopes in large cohorts of subjects with chronic and spontaneously resolved HCV viremia. Following in vitro stimulation of PBMC, HCV-specific cell cultures from each subject were screened with an overlapping panel of synthetic 20-mer peptides spanning the entire HCV polyprotein. Of 22 subjects who spontaneously controlled HCV viremia, all recognized at least one of a group of six epitopes situated within the nonstructural (NS) proteins NS3, NS4, and NS5, each of which was detected by >30% of subjects, but most subjects recognized additional, more heterogeneous specificities. In contrast, none of the most frequently targeted epitopes was detected by >5% of persons with chronic infection. The most frequently recognized peptides showed promiscuous binding to multiple HLA-DR molecules in in vitro binding assays and were restricted by different HLA-DR molecules in functional assays in different persons. These data demonstrate that predominant CD4(+) T cell epitopes in persons with resolved HCV infection are preferentially located in the nonstructural proteins and are immunogenic in the context of multiple class II molecules. This comprehensive characterization of CD4(+) T cell epitopes in resolved HCV infection provides important information to facilitate studies of immunopathogenesis and HCV vaccine design and evaluation.
Keywords in Portuguese
Vírus da Hepatite CInfecção
Resposta celular CD4 Th
Epitopos Dominantes e Altamente Promíscuos
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