Lymphocytic choriomeningitis virus infection yields overlapping CD4+ and CD8+ T-cell responses

J Virol. 2008 Dec;82(23):11734-41. doi: 10.1128/JVI.00435-08. Epub 2008 Oct 1.

Abstract

Activation of CD4(+) T cells helps establish and sustain other immune responses. We have previously shown that responses against a broad set of nine CD4(+) T-cell epitopes were present in the setting of lymphocytic choriomeningitis virus (LCMV) Armstrong infection in the context of H-2(d). This is quite disparate to the H-2(b) setting, where only two epitopes have been identified. We were interested in determining whether a broad set of responses was unique to H-2(d) or whether additional CD4(+) T-cell epitopes could be identified in the setting of the H-2(b) background. To pursue this question, we infected C57BL/6 mice with LCMV Armstrong and determined the repertoire of CD4(+) T-cell responses using overlapping 15-mer peptides corresponding to the LCMV Armstrong sequence. We confirmed positive responses by intracellular cytokine staining and major histocompatibility complex (MHC)-peptide binding assays. A broad repertoire of responses was identified, consisting of six epitopes. These epitopes originate from the nucleoprotein (NP) and glycoprotein (GP). Out of the six newly identified CD4(+) epitopes, four of them also stimulate CD8(+) T cells in a statistically significant manner. Furthermore, we assessed these CD4(+) T-cell responses during the memory phase of LCMV Armstrong infection and after infection with a chronic strain of LCMV and determined that a subset of the responses could be detected under these different conditions. This is the first example of a broad repertoire of shared epitopes between CD4(+) and CD8(+) T cells in the context of viral infection. These findings demonstrate that immunodominance is a complex phenomenon in the context of helper responses.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Epitopes, T-Lymphocyte
  • H-2 Antigens / metabolism
  • Interferon-gamma / biosynthesis
  • Lymphocytic Choriomeningitis / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data

Substances

  • Epitopes, T-Lymphocyte
  • H-2 Antigens
  • Interferon-gamma