The outcome of cross‐priming during virus infection is not directly linked to the ability of the antigen to be cross‐presented

Abstract

The initiation of CD8 1 T cell (CTL) immune responses can occur via cross-priming. Recent data suggested a relationship between cross-presentation and immunodominance of epitope-specific T cells. To test this association, we evaluated the efficacy of crosspresentation for several virus epitopes in vitro and examined if this can be extrapolated in vivo. Employing lymphocytic choriomeningitis virus (LCMV), we demonstrate that the cross-presentation and cross-priming of LCMV antigens were dominated by NP396, but not NP205 when analyzing the LCMV-NP. Although with LCMV-GP, cross-presentation was dominated by GP276, and cross-priming was dominated by GP33. Importantly, although NP396 was significantly more efficient than GP33 in cross-presentation, cross-priming of their specific CTL was comparable. In a subsequent virus challenge after cross-priming, GP33-specific CTL dominated the response. Accordingly, based on our data, the ability of viral epitopes to be cross-presented in vitro does not entirely reflect what would occur in cross-priming. Thus, weak cross-presenting antigens may still cross-prime an efficient CTL response depending on other in vivo elements such as the naïve T-cell precursor frequencies.

CD8 + T Cell Immunodominance in Lymphocytic Choriomeningitis Virus Infection Is Modified in the Presence of Toll-Like Receptor Agonists

“…In another study, cross-presentation was observed only for immunodominant epitopes (22). Moreover, using the lymphocytic choriomeningitis virus (LCMV) infection model, we observed better cross-presentation for LCMV-nucleoprotein 396 (NP396) than for LCMV-glycoprotein 33 (GP33); both epitopes are immunodominant after virus infection (2). However, the cross-priming of both epitopes was comparable in vivo due to the high GP33 T cell precursor frequency (2).…”

“…BMDC preparations were described previously, and cells were used 7 days after culturing. HEK293 or HEK-NP was used as antigen donor cells as previously described (2,5). All media were purchased from Invitrogen (Ontario, Canada).…”

“…Moreover, using the lymphocytic choriomeningitis virus (LCMV) infection model, we observed better cross-presentation for LCMV-nucleoprotein 396 (NP396) than for LCMV-glycoprotein 33 (GP33); both epitopes are immunodominant after virus infection (2). However, the cross-priming of both epitopes was comparable in vivo due to the high GP33 T cell precursor frequency (2). Thus, certain viral epitopes need to be cross-presented to attain a high position in the immunodominance hierarchy (2,21,22).…”

“…However, the cross-priming of both epitopes was comparable in vivo due to the high GP33 T cell precursor frequency (2). Thus, certain viral epitopes need to be cross-presented to attain a high position in the immunodominance hierarchy (2,21,22). However, how this phenomenon is affected in the presence of microbial stimulation is unknown.…”

“…Here, cells were induced to undergo death by LYUV treatment by subjecting cells to one round of freezethaw (liquid N 2 ) followed by UVB radiation at an intensity of 200,000 J/cm 2 for 10 min using a CL-1000 M UV cross-linker (Ultra-Violet Products Ltd., Cambridge, United Kingdom). To test for cross-priming, mice were injected with LYUV HEK-NP cells (7 ϫ 10 6 ) and TLR-L. After 7 days, epitope-specific CTLs were quantified by performing ICS as previously described (2,5).…”