title: Defining immune engagement thresholds for in vivo control of virus-driven lymphoproliferation.
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.
authors: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
authors: Cristina
authors: C
authors: Godinho-Silva
authors: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
authors: Sofia
authors: S
authors: Marques
authors: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
authors: Diana
authors: D
authors: Fontinha
authors: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
authors: Henrique
authors: H
authors: Veiga-Fernandes
authors: Sir Albert Sakzewski Virus Research Center and Queensland and Children's Medical Research Institute, University of Queensland, Brisbane, Queensland, Australia.
authors: Philip G
authors: PG
authors: Stevenson
authors: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
authors: J Pedro
authors: JP
authors: Simas
mesh_terms: D016475:3T3 Cells; D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D006224:Cricetinae; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D006566:Herpesviridae Infections / Q000276:immunology* / Q000821:virology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000096:biosynthesis / Q000276:immunology; D018144:Rhadinovirus / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D017735:Virus Latency / Q000235:genetics / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D010047:Ovalbumin