Dissecting the multifactorial causes of immunodominance in class I-restricted T cell responses to viruses

Immunity. 2000 Jan;12(1):83-93. doi: 10.1016/s1074-7613(00)80161-2.

Abstract

Following influenza virus infection, the numbers of mouse TCD8+ cells responding to five different determinants vary more than 50-fold in primary responses but less so in secondary responses. Surprisingly, each determinant elicits a highly diverse and highly sensitive TCD8+ response. Inefficient antigen processing by virus-infected cells accounts for the poor immunogenicity of just one of the subdominant determinants. Overexpressing class I-peptide complexes using vaccinia virus revealed that the poor immunogenicity of two subdominant determinants reflects limitations in T cell responses unrelated to TCR diversity or sensitivity. Despite greatly enhanced expression, the immunodominant determinant is actually less immunogenic when overexpressed by vaccinia virus. Immunodominance is also modulated by determinant-specific variations in the capacity of TCD8+ to suppress responses to other determinants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / virology
  • Cell Line
  • Disease Models, Animal
  • H-2 Antigens / genetics
  • H-2 Antigens / immunology*
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology*
  • Humans
  • Immunodominant Epitopes / immunology*
  • Influenza A virus / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Nucleoproteins / immunology*
  • Peptides / immunology
  • RNA-Binding Proteins*
  • Viral Core Proteins / immunology*

Substances

  • H-2 Antigens
  • H-2K(K) antigen
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Immunodominant Epitopes
  • NP protein, Influenza A virus
  • Nucleoproteins
  • Peptides
  • RNA-Binding Proteins
  • Viral Core Proteins