V3 CTL epitope density in a single recombinant molecule antigen differentially affects the number and activity of primary and memory CD8+ T cells

Vaccine. 2008 Feb 6;26(6):845-52. doi: 10.1016/j.vaccine.2007.11.022. Epub 2007 Nov 29.

Abstract

Previous studies have found the close correlation between epitope density and epitope-specific response, which have shown that high epitope density in a single recombinant protein molecule significantly enhances the humoral response and protective immunity. However, it has not been determined whether this kind of high epitope density could also significantly influence T cell response. Based on this, a series of recombinant DNA and proteins were designed and prepared. Each molecule consists of various copy numbers of the V3 CTL epitope on HIV-1 gp120 (one, two, four and eight copies). Our results show clearly that different V3-epitope densities in just one single DNA or protein molecules have respectively different effects on the number and activity of both primary and memory T cells. Interestingly, this effect is more complex than that on the B cells: epitope density in one plasmid or protein antigen affects the number, not the cytotoxic avidity, of primary CD8+ T cells, but affects both the number and cytotoxic avidity of memory CD8+ T cells. It indicates epitope density in the antigen is an important consideration to optimize T cell response induction and may facilitate the development of effective T cell-based anti-virus vaccines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / immunology*
  • Animals
  • Cytotoxicity Tests, Immunologic
  • Epitopes, T-Lymphocyte / immunology*
  • HIV Envelope Protein gp120 / immunology*
  • HIV Infections / immunology*
  • HIV-1 / immunology*
  • Immunologic Memory / immunology*
  • Lymphocyte Count
  • Mice
  • Mice, Inbred BALB C
  • Peptide Fragments / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Vaccines, DNA / immunology

Substances

  • AIDS Vaccines
  • Epitopes, T-Lymphocyte
  • HIV Envelope Protein gp120
  • HIV envelope protein gp120 (305-321)
  • Peptide Fragments
  • Vaccines, DNA