Multiple antigen-specific processing pathways for activating naive CD8+ T cells in vivo

C. C. Norbury, M. F. Princiotta, I. Bacik, Randy Brutkiewicz, P. Wood, T. Elliott, J. R. Bennink, J. W. Yewdell

Research output: Contribution to journalArticle

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Abstract

Current knowledge of the processing of viral Ags into MHC class I-associated ligands is based almost completely on in vitro studies using nonprofessional APCs (pAPCs). This is two steps removed from real immune responses to pathogens and vaccines, in which pAPCs activate naive CD8+ T cells in vivo. Rational vaccine design requires answers to numerous questions surrounding the function of pAPCs in vivo, including their abilities to process and present peptides derived from endogenous and exogenous viral Ags. In the present study, we characterize the in vivo dependence of Ag presentation on the expression of TAP by testing the immunogenicity of model Ags synthesized by recombinant vaccinia viruses in TAP1-/- mice. We show that the efficiency of TAP-independent presentation in vitro correlates with TAP-independent activation of naive T cells in vivo and provide the first in vivo evidence for proteolytic processing of antigenic peptides in the secretory pathway. There was, however, a clear exception to this correlation; although the presentation of the minimal SIINFEKL determinant from chicken egg OVA in vitro was strictly TAP dependent, it was presented in a TAP-independent manner in vivo. In vivo presentation of the same peptide from a fusion protein retained its TAP dependence. These results show that determinant-specific processing pathways exist in vivo for the generation of antiviral T cell responses. We present additional findings that point to cross-priming as the likely mechanism for these protein-specific differences.

Original languageEnglish (US)
Pages (from-to)4355-4362
Number of pages8
JournalJournal of Immunology
Volume166
Issue number7
StatePublished - Apr 1 2001
Externally publishedYes

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Antigen Presentation
T-Lymphocytes
Peptides
Vaccines
Cross-Priming
Vaccinia virus
Secretory Pathway
Antiviral Agents
Ovum
Chickens
Proteins
Ligands
In Vitro Techniques

ASJC Scopus subject areas

  • Immunology

Cite this

Norbury, C. C., Princiotta, M. F., Bacik, I., Brutkiewicz, R., Wood, P., Elliott, T., ... Yewdell, J. W. (2001). Multiple antigen-specific processing pathways for activating naive CD8+ T cells in vivo. Journal of Immunology, 166(7), 4355-4362.

Multiple antigen-specific processing pathways for activating naive CD8+ T cells in vivo. / Norbury, C. C.; Princiotta, M. F.; Bacik, I.; Brutkiewicz, Randy; Wood, P.; Elliott, T.; Bennink, J. R.; Yewdell, J. W.

In: Journal of Immunology, Vol. 166, No. 7, 01.04.2001, p. 4355-4362.

Research output: Contribution to journalArticle

Norbury, CC, Princiotta, MF, Bacik, I, Brutkiewicz, R, Wood, P, Elliott, T, Bennink, JR & Yewdell, JW 2001, 'Multiple antigen-specific processing pathways for activating naive CD8+ T cells in vivo', Journal of Immunology, vol. 166, no. 7, pp. 4355-4362.
Norbury CC, Princiotta MF, Bacik I, Brutkiewicz R, Wood P, Elliott T et al. Multiple antigen-specific processing pathways for activating naive CD8+ T cells in vivo. Journal of Immunology. 2001 Apr 1;166(7):4355-4362.
Norbury, C. C. ; Princiotta, M. F. ; Bacik, I. ; Brutkiewicz, Randy ; Wood, P. ; Elliott, T. ; Bennink, J. R. ; Yewdell, J. W. / Multiple antigen-specific processing pathways for activating naive CD8+ T cells in vivo. In: Journal of Immunology. 2001 ; Vol. 166, No. 7. pp. 4355-4362.
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