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

• Published in: PLoS pathogens Vol. 10; no. 6; p. e1004220
• Main Authors: Godinho-Silva, Cristina, Marques, Sofia, Fontinha, Diana, Veiga-Fernandes, Henrique, Stevenson, Philip G., Simas, J Pedro
• Format: Journal Article
• Language: English
• Published: United States PLOS 01.06.2014; Public Library of Science; Public Library of Science (PLoS)
• Subjects: 3T3 Cells; Adoptive Transfer; Animals; Antigenic determinants; Antigens; B cells; Biology and life sciences; CD4-Positive T-Lymphocytes - immunology; Cell Proliferation; Cells, Cultured; Cricetinae; Distribution; Epitopes, T-Lymphocyte - genetics; Epitopes, T-Lymphocyte - immunology; Health aspects; Herpesviridae Infections - immunology; Herpesviridae Infections - virology; Herpesviruses; Histocompatibility Antigens Class I - immunology; Immune system; Immunoglobulins; Ligands; Lymphocyte Activation - immunology; Medical research; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Ovalbumin - biosynthesis; Ovalbumin - immunology; Physiological aspects; Rhadinovirus - genetics; Rhadinovirus - immunology; T cell receptors; T cells; T-Lymphocytes, Cytotoxic - immunology; Vaccines; Virus Latency - genetics; Virus Latency - immunology
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1004220

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. 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. JPS was funded by Fundação para a Ciência e Tecnologia (PTDC/SAU-MII/099314/2008); HMSP-ICT/0021/2010) Portugal. CGS, SM, and DF were supported by scholarships from Fundação para a Ciência e Tecnologia, Portugal. PGS is an ARC Future Fellow.