Kinetics of major histocompatibility class I antigen presentation in acute infection

J Immunol. 2009 Jan 15;182(2):902-11. doi: 10.4049/jimmunol.182.2.902.

Abstract

Ag presentation within the regional lymph node is crucial for the initiation of CD8+ T cell responses following viral infection. The magnitude and quality of the CD8+ T cell response are regulated by the interplay between the size of the APC population and duration of Ag presentation. To understand how these parameters are finely regulated during an immune response, we have investigated the dynamics of Ag presentation in influenza A virus and HSV-1 infection. In both infections, APC production was calculated to occur over the first few days of infection, after which there was slow exponential decay over a period of up to 2 wk. This production rate is most likely determined by the Ag availability and recruitment and/or maturation rate of dendritic cells. APC production was found to closely parallel lymph node cell recruitment in both infections. This was greatest in the first 6 h of infection for HSV and over the second and third day for influenza. In HSV infection, the peak production also coincides with peak viral levels. By contrast, in influenza infection, APC production ceased between the third and fourth day despite the presence of high levels of virus until 5 days after infection. These analyses demonstrate that two quite different self-limiting infections generate the APC necessary to drive T cell responses early in infection at different rates. Understanding how such contrasting kinetics of Ag presentation impacts on the growth and size of developing protective T cell populations has important implications for the design of vaccines and immunotherapies.

Publication types

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

MeSH terms

  • Acute Disease
  • Animals
  • Antigen Presentation / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / virology
  • Cell Movement / immunology
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Dendritic Cells / virology
  • H-2 Antigens / immunology*
  • H-2 Antigens / metabolism
  • Herpes Simplex / immunology*
  • Herpes Simplex / pathology
  • Herpes Simplex / virology
  • Herpesvirus 1, Human / immunology*
  • Histocompatibility Antigen H-2D
  • Influenza A Virus, H3N2 Subtype / immunology*
  • Leukocyte Count / statistics & numerical data
  • Linear Models
  • Lymph Nodes / immunology
  • Lymph Nodes / pathology
  • Lymph Nodes / virology
  • Mice
  • Mice, Inbred C57BL
  • Models, Immunological
  • Orthomyxoviridae Infections / immunology*
  • Orthomyxoviridae Infections / pathology
  • Orthomyxoviridae Infections / virology
  • Peptide Fragments / immunology*
  • Peptide Fragments / metabolism
  • Viral Core Proteins / immunology*
  • Viral Core Proteins / metabolism

Substances

  • H-2 Antigens
  • H-2Kb protein, mouse
  • Histocompatibility Antigen H-2D
  • Peptide Fragments
  • Viral Core Proteins
  • nucleoprotein (366-374), influenza virus