%0 Journal Article
%T Defining Immune Engagement Thresholds for In Vivo Control of Virus-Driven Lymphoproliferation
%A Cristina Godinho-Silva equal contributor
%A Sofia Marques equal contributor
%A Diana Fontinha
%A Henrique Veiga-Fernandes
%A Philip G. Stevenson
%A J. Pedro Simas
%J PLOS Pathogens
%D 2014
%I Public Library of Science (PLoS)
%R doi/10.1371/journal.ppat.1004220
%X 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 ¦Ã-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.
%U http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1004220