CD8+ T-cells play a crucial role in eradicating viral infections. The focus of this project is two-fold. First, to study general in vivo mechanisms of virus - host interactions and second, to understand how primary and memory T-cells respond to virus infection. Despite the importance of T-cells, we do not yet fully understand the induction of a CD8+ T-cell responses and the generation of CD8+ T-cell memory to virus infection. For viruses in which traditional vaccine approaches have not been successful, it is hoped that induction of CD8+ T-cell memory will enhance immunity. To induce optimal CD8+ T-cell responses to vaccines it is necessary to understand how primary CD8+ T-cells are stimulated. This project aims to address questions related to the optimal and activation of T cell immunity following primary and secondary virus infection by studying several viruses and different routes of infection. This year our studies examining a poxvirus skin infection have demonstrated distinct roles for innate and adaptive immune cells in virus clearance.

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Yang, Ning; Gibbs, James S; Hickman, Heather D et al. (2016) Defining Viral Defective Ribosomal Products: Standard and Alternative Translation Initiation Events Generate a Common Peptide from Influenza A Virus M2 and M1 mRNAs. J Immunol 196:3608-17
Cush, Stephanie S; Reynoso, Glennys V; Kamenyeva, Olena et al. (2016) Locally Produced IL-10 Limits Cutaneous Vaccinia Virus Spread. PLoS Pathog 12:e1005493
Filardy, A A; He, J; Bennink, J et al. (2016) Posttranscriptional control of NLRP3 inflammasome activation in colonic macrophages. Mucosal Immunol 9:850-8
Frank, Gregory M; Angeletti, Davide; Ince, William L et al. (2015) A Simple Flow-Cytometric Method Measuring B Cell Surface Immunoglobulin Avidity Enables Characterization of Affinity Maturation to Influenza A Virus. MBio 6:e01156
Altman, Meghan O; Bennink, Jack R; Yewdell, Jonathan W et al. (2015) Lamprey VLRB response to influenza virus supports universal rules of immunogenicity and antigenicity. Elife 4:
Whittle, James R R; Wheatley, Adam K; Wu, Lan et al. (2014) Flow cytometry reveals that H5N1 vaccination elicits cross-reactive stem-directed antibodies from multiple Ig heavy-chain lineages. J Virol 88:4047-57
Gilchuk, Pavlo; Spencer, Charles T; Conant, Stephanie B et al. (2013) Discovering naturally processed antigenic determinants that confer protective T cell immunity. J Clin Invest 123:1976-87
Yu, Cheng-Rong; Dambuza, Ivy M; Lee, Yong-Jun et al. (2013) STAT3 regulates proliferation and survival of CD8+ T cells: enhances effector responses to HSV-1 infection, and inhibits IL-10+ regulatory CD8+ T cells in autoimmune uveitis. Mediators Inflamm 2013:359674
Hickman, Heather D; Yewdell, Jonathan W (2013) Going Pro to enhance T-cell immunogenicity: easy as ýý? Eur J Immunol 43:2814-7
Hickman, Heather D; Reynoso, Glennys V; Ngudiankama, Barbara F et al. (2013) Anatomically restricted synergistic antiviral activities of innate and adaptive immune cells in the skin. Cell Host Microbe 13:155-68

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