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Shane Crotty, Magdalini Moutaftsi, Megan McCausland, D Huw Davies, Juan Moyron Quiroz, Robert Johnston, Rafii Mohammed Benhnia, Howard Grey, Julia Hoffmann, Steven Head, David Garboczi, Alessandro Sette, Deterministic linkage between CD4 T cell and B cell specificities to a large virus: vaccinia virus (43.1), The Journal of Immunology, Volume 178, Issue 1_Supplement, April 2007, Page S36, https://doi.org/10.4049/jimmunol.178.Supp.43.1
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Abstract
Antibody responses are critical components of protective immune responses to many pathogens, but it remains unclear what parameters determine which pathogen proteins are targeted. We have performed large scale studies to map mouse antibody and CD4 T cell responses to the smallpox vaccine virus, vaccinia. Our analysis of this large virus ( > 200 genes) identified 13 viral protein targets of CD4 T cell responses and 23 antibody targets. Unexpectedly, nearly half of the CD4 T cell responses targeted the same viral virion proteins as the antibody responses, suggesting a deterministic linkage between the specificities. Immunizing mice with individual MHC II epitopes revealed that, after viral infection, help between CD4 T cells and B cells of matched viral virion protein specificity is largely non-transferrable to other virion proteins. We used this knowledge to then predict the presence of new MHC II epitopes. In total, 11 of the 18 CD4 T cell responses (61%) we identified were matched by a paired antibody response to the same protein, including all of the top 5 viral protein IgG targets. These data demonstrate that MHC restriction at the protein level is a critical event for anti-virion antibodies to a large virus. This is a powerful predictive principle and is of general relevance for understanding the nature of B cell antigen presentation to CD4 T cells against complex pathogens. NIH-AI-63107
