Coxsackievirus B3 inhibits antigen presentation in vivo, exerting a profound and selective effect on the MHC class I pathway.
Many viruses encode proteins whose major function is to evade or disable the host T cell response. Nevertheless, most viruses are readily detected by host T cells, and induce relatively strong T cell responses. Herein, we employ transgenic CD4(+) and CD8(+) T cells as sensors to evaluate in vitro and in vivo antigen presentation by coxsackievirus B3 (CVB3), and we show that this virus almost completely inhibits antigen presentation via the MHC class I pathway, thereby evading CD8(+) T cell immunity. In contrast, the presentation of CVB3-encoded MHC class II epitopes is relatively unencumbered, and CVB3 induces in vivo CD4(+) T cell responses that are, by several criteria, phenotypically normal. The cells display an effector phenotype and mature into multi-functional CVB3-specific memory CD4(+) T cells that expand dramatically following challenge infection and rapidly differentiate into secondary effector cells capable of secreting multiple cytokines. Our findings have implications for the efficiency of antigen cross-presentation during coxsackievirus infection.
Kemball
Christopher C
CC
Department of Immunology and Microbial Science, SP30-2110, The Scripps Research Institute, La Jolla, CA, USA.
Harkins
Stephanie
S
Whitmire
Jason K
JK
Flynn
Claudia T
CT
Feuer
Ralph
R
Whitton
J Lindsay
JL
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002478:Cells, Cultured; D003384:Coxsackievirus Infections / Q000276:immunology; D029822:Enterovirus B, Human / Q000276:immunology / Q000502:physiology*; D000939:Epitopes / Q000276:immunology; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology
D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D011948:Receptors, Antigen, T-Cell