The induction of virus-specific CTL as a function of increasing epitope expression: responses rise steadily until excessively high levels of epitope are attained

J Immunol. 1999 Oct 1;163(7):3735-45.

Abstract

The role of epitope expression levels in CD8+ T cell priming has been controversial. Yet this parameter is of great importance in the design of rational approaches to optimize CTL responses to a variety of pathogens. In this paper we examine the influence of epitope production on CD8+ T cell priming by exploiting a system that allows a 200-fold range of cell surface epitope expression in vitro with a fixed dose of vaccinia virus. Our results demonstrate that, with the exception of a notable decline at the highest level of epitope, the magnitude of the responding CTL population generated in vivo following equivalent viral infections is essentially proportional to epitope density.

Publication types

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

MeSH terms

  • Animals
  • Antigens, Surface / metabolism
  • Antigens, Viral / biosynthesis
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology*
  • Cytotoxicity, Immunologic
  • Dose-Response Relationship, Immunologic
  • Egg Proteins / genetics
  • Egg Proteins / immunology
  • Epitopes, T-Lymphocyte / biosynthesis*
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / metabolism
  • Female
  • Hybridomas
  • Influenza A virus / immunology
  • L Cells
  • Lymphocyte Activation
  • Lymphocyte Count
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Nucleocapsid Proteins
  • Nucleoproteins / biosynthesis
  • Nucleoproteins / genetics
  • Nucleoproteins / immunology
  • Ovalbumin / genetics
  • Ovalbumin / immunology
  • Peptide Fragments
  • RNA-Binding Proteins*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism*
  • T-Lymphocytes, Cytotoxic / virology
  • Vaccinia virus / genetics
  • Vaccinia virus / immunology
  • Viral Core Proteins / biosynthesis
  • Viral Core Proteins / genetics
  • Viral Core Proteins / immunology
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology

Substances

  • Antigens, Surface
  • Antigens, Viral
  • Egg Proteins
  • Epitopes, T-Lymphocyte
  • NP protein, Influenza A virus
  • Nucleocapsid Proteins
  • Nucleoproteins
  • OVA-8
  • Peptide Fragments
  • RNA-Binding Proteins
  • Viral Core Proteins
  • Viral Vaccines
  • Ovalbumin