Defining immune engagement thresholds for in vivo control of virus-driven lymphoproliferation

Godinho-Silva, Cristina; Marques, Sofia; Fontinha, Diana; Veiga-Fernandes, Henrique; Stevenson, Philip G.; Simas, J Pedro

http://hdl.handle.net/10451/51219

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Autores

Godinho-Silva, Cristina

Marques, Sofia

Fontinha, Diana

Veiga-Fernandes, Henrique

Stevenson, Philip G.

Simas, J Pedro

Resumo(s)

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.

Descrição

Copyright: © 2014 Godinho-Silva et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.