Cross-priming utilizes antigen not available to the direct presentation pathway

Keri B. Donohue, Jean M. Grant, Eric F. Tewalt, Douglas C. Palmer, Marc R. Theoret, Nicholas P. Restifo, Christopher C. Norbury

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

CD8+ T cells play a crucial role in protective immunity to viruses and tumours. Antiviral CD8+ T cells are initially activated by professional antigen presenting cells (pAPCs) that are directly infected by viruses (direct-priming) or following uptake of exogenous antigen transferred from virus-infected or tumour cells (cross-priming). In order to efficiently target each of these antigen-processing pathways during vaccine design, it is necessary to delineate the properties of the natural substrates for either of these antigen-processing pathways. In this study, we utilized a novel T-cell receptor (TCR) transgenic mouse to examine the requirement for both antigen synthesis and synthesis of other cellular factors during direct or cross-priming. We found that direct presentation required ongoing synthesis of antigen, but that cross-priming favoured long-lived antigens and did not require ongoing antigen production. Even after prolonged blockade of protein synthesis in the donor cell, cross-priming was unaffected. In contrast, direct-presentation was almost undetectable in the absence of antigen neosynthesis and required ongoing protein synthesis. This suggests that the direct- and cross-priming pathways may utilize differing pools of antigen, an observation that has far-reaching implications for the rational design of vaccines aimed at the generation of protective CD8+ T cells.

Original languageEnglish (US)
Pages (from-to)63-73
Number of pages11
JournalImmunology
Volume119
Issue number1
DOIs
StatePublished - Sep 2006

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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