Defining Immune Engagement Thresholds for In Vivo Control of Virus-Driven Lymphoproliferation |
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| Authors: | Cristina Godinho-Silva Sofia Marques Diana Fontinha Henrique Veiga-Fernandes Philip G. Stevenson J. Pedro Simas |
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| Affiliation: | 1. Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.; 2. Sir Albert Sakzewski Virus Research Center and Queensland and Children''s Medical Research Institute, University of Queensland, Brisbane, Queensland, Australia.; Dartmouth Medical School, United States of America, |
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| Abstract: | 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. |
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