Conserved hierarchy of helper T cell responses in a chimpanzee during primary and secondary hepatitis C virus infections

J Immunol. 2004 Jan 1;172(1):483-92. doi: 10.4049/jimmunol.172.1.483.

Abstract

Control of hepatitis C virus (HCV) infection could be influenced by the timing and magnitude of CD4+ T cell responses against individual epitopes. We characterized CD4+ T cells targeting seven Pan troglodytes (Patr) class II-restricted epitopes during primary and secondary HCV infections of a chimpanzee. All Patr-DR-restricted HCV epitopes bound multiple human HLA-DR molecules, indicating the potential for overlap in epitopes targeted by both species. Some human MHC class II molecules efficiently stimulated IL-2 production by chimpanzee virus-specific T cell clones. Moreover, one conserved epitope designated NS3(1248) (GYKVLVLNPSV) overlapped a helper epitope that is presented by multiple HLA-DR molecules in humans who spontaneously resolved HCV infection. Resolution of primary infection in the chimpanzee was associated with an initial wave of CD4+ T cells targeting a limited set of dominant epitopes including NS3(1248.) A second wave of low-frequency CD4+ T cells targeting other subdominant epitopes appeared in blood several weeks later after virus replication was mostly contained. During a second infection 7 years later, CD4+ T cells against all epitopes appeared in blood sooner and at higher frequencies but the pattern of dominance was conserved. In summary, primary HCV infection in this individual was characterized by T cell populations targeting two groups of MHC class II-restricted epitopes that differed in frequency and kinetics of appearance in blood. The hierarchial nature of the CD4+ T cell response, if broadly applicable to other HCV-infected chimpanzees and humans, could be a factor governing the outcome of HCV infection.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigen Presentation
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / virology
  • Cell Line, Transformed
  • Clone Cells
  • Conserved Sequence*
  • Epitopes, T-Lymphocyte / administration & dosage
  • Epitopes, T-Lymphocyte / blood
  • Epitopes, T-Lymphocyte / immunology*
  • Hepacivirus / immunology*
  • Hepatitis C / immunology*
  • Hepatitis C / virology
  • Histocompatibility Antigens Class I / administration & dosage
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / metabolism
  • Histocompatibility Antigens Class II / administration & dosage
  • Histocompatibility Antigens Class II / immunology
  • Histocompatibility Antigens Class II / metabolism
  • Humans
  • Immunization, Secondary
  • Immunodominant Epitopes / administration & dosage
  • Immunodominant Epitopes / blood
  • Immunodominant Epitopes / immunology
  • Liver / immunology
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Molecular Sequence Data
  • Pan troglodytes
  • Peptide Mapping
  • Sequence Homology, Amino Acid
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / virology*
  • Vaccination
  • Viral Nonstructural Proteins / immunology
  • Viral Nonstructural Proteins / metabolism

Substances

  • Epitopes, T-Lymphocyte
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Immunodominant Epitopes
  • Viral Nonstructural Proteins
  • NS-5 protein, hepatitis C virus