CTL response compensation for the loss of an immunodominant class I-restricted HSV-1 determinant

Immunol Cell Biol. 2006 Dec;84(6):543-50. doi: 10.1111/j.1440-1711.2006.01469.x. Epub 2006 Sep 5.

Abstract

The T-cell response to even complex pathogens is often focused on only a handful of immunodominant determinants. Such narrow responses provoke a selective pressure that can drive the emergence of CTL escape variants, raising the question of whether a broader response, targeting multiple non-dominant peptides may be more beneficial. To examine the ability of the T-cell repertoire to respond to non-dominant determinants, we have investigated how mutating the dominant peptide in HSV affects the magnitude of the CD8+ T-cell response. We found that the CTL response to HSV lacking the dominant peptide was only modestly reduced compared with the wild-type virus and, surprisingly, this compensation occurred without any enhancement in the response to an established minor epitope. These findings are supportive of a malleable T-cell repertoire that can elicit strong responses to alternate, unknown determinants in the absence of the dominant response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Herpesvirus 1, Human / genetics
  • Herpesvirus 1, Human / immunology*
  • Herpesvirus 1, Human / physiology*
  • Immunodominant Epitopes / genetics*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / physiology*
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology*
  • Virus Replication

Substances

  • Immunodominant Epitopes
  • Viral Envelope Proteins
  • glycoprotein B, Simplexvirus