Abstract
Many viruses encode proteins whose major function is to evade or disable the host T cell response. Nevertheless, most viruses are readily detected by host T cells, and induce relatively strong T cell responses. Herein, we employ transgenic CD4+ and CD8+ T cells as sensors to evaluate in vitro and in vivo antigen presentation by coxsackievirus B3 (CVB3), and we show that this virus almost completely inhibits antigen presentation via the MHC class I pathway, thereby evading CD8+ T cell immunity. In contrast, the presentation of CVB3-encoded MHC class II epitopes is relatively unencumbered, and CVB3 induces in vivo CD4+ T cell responses that are, by several criteria, phenotypically normal. The cells display an effector phenotype and mature into multi-functional CVB3-specific memory CD4+ T cells that expand dramatically following challenge infection and rapidly differentiate into secondary effector cells capable of secreting multiple cytokines. Our findings have implications for the efficiency of antigen cross-presentation during coxsackievirus infection.
Highlights
Most virus infections are potent inducers of T cell activation and expansion, and viruses employ several strategies to elude these T cell responses
CVB-specific T cell responses, we generated a recombinant coxsackievirus B3 (CVB3) that expresses well-characterized CD8+ and CD4+ T cell epitopes derived from lymphocytic choriomeningitis virus (LCMV)
Because native murine T cell epitopes have not been identified for CVB3, we constructed a series of recombinant CVB3 (Table 1) that encode well characterized CD8+ and/or CD4+ T cell epitopes derived from lymphocytic choriomeningitis virus (LCMV)
Summary
Most virus infections are potent inducers of T cell activation and expansion, and viruses employ several strategies to elude these T cell responses. Still more viruses – for example, the poxviruses – encode factors that inhibit or misdirect the effector functions of T cells. Despite these immunoevasion strategies, in the great majority of acute virus infections that have been studied T cell responses are readily detected directly ex vivo. In the great majority of acute virus infections that have been studied T cell responses are readily detected directly ex vivo This is not to say that the evasive factors encoded by these viruses have no in vivo effect, but rather the virus’ ability to evade host T cell responses is far from complete.
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