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

The initiation of CD8⁺ 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 cross‐presentation 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.