Immunodominant west nile virus t cell epitopes are fewer in number and fashionably late

Saghar Kaabinejadian, Curtis P. McMurtrey, Sojung Kim, Rinki Jain, Wilfried Bardet, Fredda B. Schafer, Jason L. Davenport, Aaron D. Martin, Michael S. Diamond, Jon A. Weidanz, Ted H. Hansen, William H. Hildebrand

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8 Scopus citations

Abstract

Class I HLA molecules mark infected cells for immune targeting by presenting pathogen-encoded peptides on the cell surface. Characterization of viral peptides unique to infected cells is important for understanding CD8+ T cell responses and for the development of T cell-based immunotherapies. Having previously reported a series of West Nile virus (WNV) epitopes that are naturally presented by HLA-A∗02:01, in this study we generated TCR mimic (TCRm) mAbs to three of these peptide/HLA complexes-the immunodominant SVG9 (E protein), the subdominant SLF9 (NS4B protein), and the immunorecessive YTM9 (NS3 protein)-and used these TCRm mAbs to stain WNV-infected cell lines and primary APCs. TCRm staining of WNV-infected cells demonstrated that the immunorecessive YTM9 appeared several hours earlier and at 5-to 10-fold greater density than the more immunogenic SLF9 and SVG9 ligands, respectively. Moreover, staining following inhibition of the TAP demonstrated that all three viral ligands were presented in a TAP-dependent manner despite originating from different cellular compartments. To our knowledge, this study represents the first use of TCRm mAbs to define the kinetics and magnitude of HLA presentation for a series of epitopes encoded by one virus, and the results depict a pattern whereby individual epitopes differ considerably in abundance and availability. The observations that immunodominant ligands can be found at lower levels and at later time points after infection suggest that a reevaluation of the factors that combine to shape T cell reactivity may be warranted.

Original languageEnglish
Pages (from-to)4263-4273
Number of pages11
JournalJournal of Immunology
Volume196
Issue number10
DOIs
StatePublished - May 15 2016

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    Kaabinejadian, S., McMurtrey, C. P., Kim, S., Jain, R., Bardet, W., Schafer, F. B., Davenport, J. L., Martin, A. D., Diamond, M. S., Weidanz, J. A., Hansen, T. H., & Hildebrand, W. H. (2016). Immunodominant west nile virus t cell epitopes are fewer in number and fashionably late. Journal of Immunology, 196(10), 4263-4273. https://doi.org/10.4049/jimmunol.1501821