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The aging immune system reveals the biological impact of direct antigen presentation on CD8 T cell responses #MMPMID28615415
Uhrlaub JL; Smithey MJ; Nikolich-?ugich J
J Immunol 2017[Jul]; 199 (2): 403-7 PMID28615415show ga
The vertebrate immune system employs multiple, sometimes redundant, mechanisms to contain pathogenic microorganisms that are always evolving to evade host defenses. Thus, the cowpox virus (CPXV) uses genes encoding CPXV12 and CPXV203 to prevent direct MHCI presentation of viral peptides by infected cells. However, CD8 T cells are effectively primed against CPXV by cross-presentation of viral antigens in young mice. Old mice accumulate defects in both CD8 T cell activation and cross-presentation. Using a double-deletion mutant (?12?203) of CPXV, we show that direct priming of CD8 T cells in old mice yields superior recall responses, establishing a key contribution of this mechanism to host anti-poxvirus responses and enhancing our fundamental understanding of how viral manipulation of direct presentation impacts pathogenesis. This also provides a proof of principle that suboptimal CD8 T cell in old organisms can be optimized by manipulating antigen presentation, with implications for vaccine design.