Defining Immune Engagement Thresholds for in Vivo Control of Virus-Driven Lymphoproliferation

Persistent infections are subject to constant surveillance by cd8+ cytotoxic t cells (ctl). their control should therefore depend on mhc class i-restricted epitope presentation. many epitopes are described for γ-herpesviruses and form a basis for prospective immunotherapies and vaccines. however the quantitative requirements of in vivo immune control for epitope presentation and recognition remain poorly defined. we used murid herpesvirus-4 (muhv-4) to determine for a latently expressed viral epitope how mhc class-i binding and ctl functional avidity impact on host colonization. tracking muhv-4 recombinants that differed only in epitope presentation,we found little latitude for sub-optimal mhc class i binding before immune control failed. by contrast,control remained effective across a wide range of t cell functional avidities. thus,we could define critical engagement thresholds for the in vivo immune control of virus-driven b cell proliferation. © 2014 godinho-silva et al.