Major histocompatibility complex class I-restricted cross-presentation is biased towards high dose antigens and those released during cellular destruction

Christian Kurts, Jacques F.A.P. Miller, Rathan M. Subramaniam, Francis R. Carbone, William R. Heath

Research output: Contribution to journalArticle

251 Scopus citations

Abstract

Naive T cells recirculate mainly within the secondary lymphoid compartment, but once activated they can enter peripheral tissues and perform effector functions. To activate naive T cells, foreign antigens must traffic from the site of infection to the draining lymph nodes, where they can be presented by professional antigen presenting cells. For major histocompatibility complex class I-restricted presentation to CD8+ T cells, this can occur via the cross-presentation pathway. Here, we investigated the conditions allowing antigen access to this pathway. We show that the level of antigen expressed by peripheral tissues must be relatively high to facilitate cross-presentation to naive CD8+ T cells. Below this level, peripheral antigens did not stimulate by cross-presentation and were ignored by naive CD8+ T cells, although they could sensitize tissue cells for destruction by activated cytotoxic T lymphocytes (CTLs). Interestingly, CTL-mediated tissue destruction facilitated cross-presentation of low dose antigens for activation of naive CD8+ T cells. This represents the first in vivo evidence that cellular destruction can enhance access of exogenous antigens to the cross-presentation pathway. These data indicate that the cross-presentation pathway focuses on high dose antigens and those released during tissue destruction.

Original languageEnglish (US)
Pages (from-to)409-414
Number of pages6
JournalJournal of Experimental Medicine
Volume188
Issue number2
DOIs
Publication statusPublished - Jul 20 1998

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Keywords

  • Antigen presentation
  • Antigen presenting cells
  • Apoptosis
  • CD8 T lymphocytes
  • T cell activation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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