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Cross‐priming utilizes antigen not available to the direct presentation pathway
Author(s) -
Donohue Keri B.,
Grant Jean M.,
Tewalt Eric F.,
Palmer Douglas C.,
Theoret Marc R.,
Restifo Nicholas P.,
Norbury Christopher C.
Publication year - 2006
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2006.02406.x
Subject(s) - priming (agriculture) , antigen , cross presentation , antigen processing , cytotoxic t cell , biology , t cell receptor , antigen presentation , immunology , cd8 , t cell , antigen presenting cell , microbiology and biotechnology , immune system , in vitro , biochemistry , mhc class i , botany , germination
Summary 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.