HCV epitope, homologous to multiple human protein sequences, induces a regulatory T cell response in infected patients.
J Hepatol
; 62(1): 48-55, 2015 Jan.
Article
en En
| MEDLINE
| ID: mdl-25157982
ABSTRACT
BACKGROUND & AIMS:
Spontaneous resolution of hepatitis C virus (HCV) infection depends upon a broad T cell response to multiple viral epitopes. However, most patients fail to clear infections spontaneously and develop chronic disease. The elevated number and function of CD3(+)CD4(+)CD25(+)FoxP3(+) regulatory T cells (T(reg)) in HCV-infected patients suggest a role of Treg cells in impaired viral clearance. The factors contributing to increased Treg cell activity in chronic hepatitis C cases remain to be delineated.METHODS:
Immunoinformatics tools were used to predict promiscuous, highly-conserved HLA-DRB1-restricted immunogenic consensus sequences (ICS), each composed of multiple T cell epitopes. These sequences were synthesized and added to cultures of peripheral blood mononuclear cells (PBMCs), derived from patients who resolved HCV infection spontaneously, patients with persistent infection, and non-infected individuals. The cells were collected and following 5days incubation, quantified and characterized by flow cytometry.RESULTS:
One immunogenic consensus sequence (ICS), HCV_G1_p7_794, induced a marked increase in Treg cells in PBMC cultures derived from infected patients, but not in patients who spontaneously cleared HCV or in non-infected individuals. An analogous human peptide (p7_794), on the other hand, induced a significant increase in Treg cells among PBMCs derived from both HCV-infected and non-infected individuals. JanusMatrix analyses determined that HCV_G1_p7_794 is comprised of Treg cell epitopes that exhibit extensive cross-reactivity with the human proteome.CONCLUSIONS:
A virus-encoded peptide (HCV_G1_p7_794) with extensive human homology activates cross-reactive CD3(+)CD4(+)CD25(+)FoxP3(+) natural Treg cells, which potentially contributes to immunosuppression and to the development of chronic hepatitis C.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Linfocitos T Reguladores
/
Hepacivirus
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Epítopos de Linfocito T
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Hepatitis C Crónica
/
Tolerancia Inmunológica
Tipo de estudio:
Prognostic_studies
Límite:
Adult
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Female
/
Humans
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Male
Idioma:
En
Revista:
J Hepatol
Asunto de la revista:
GASTROENTEROLOGIA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos