The goal of this core is to serve Projects 1 and 2, by identifying HLA class I and class II epitopes derived from VZV, as a necessary prelude to the analyses of the dynamics of the epitope-specific T cell responses to vaccination with the zoster vaccine (Project 2). This data generated on the epitope specific T cell responses will be critical in evaluating the innate signatures that correlate with, and predict, the magnitude of the epitope specific T cell responses in Project 1. A key question that will be facilitated by the information generated in this core, is whether early innate signatures are capable of predicting the "breadth" of the T cell responses to zoster vaccinafion in the elderly. Accordingly, our specific aims are:
Aim 1. Prediction and synthesis of candidate VZV HLA class I and class II epitopes We will screen the VZV proteome for the presence of sequence motifs associated with binding to 12 different HLA class I and 9 different HLA class II molecules, representafive of main HLA supertypes, and representative of the majority of HLA class I and class II molecules expressed in different ethnicities woridwide. Prediction of epitopes restricted by of a broad range of prevalent HLA molecules and supertypes will ensure adequate populafion coverage, thus enabling a rigorous evaluation of T cell responses associated with infecfion and vaccinafion in humans.
Aim 2. Test validated epitopes for binding to purified HLA molecules In vitro Project 2 will be mainly responsible for epitope validation and characterizafion, and as such those acfivities are neither described in detail nor budgeted for in the present secfion describing this core. In this core, we will test the validated/identified epitopes for binding to HLA molecules in vitro, thus enabling projection of their use in different ethnicities.
Aim 3. Data handling and Epitope submission In terms of submission of epitope data to the lEDB, we already have in-house the capability to prepare and submit data in the required XML format, as the proposed PI of this core is also the PI of the lEDB project. We anticipate being able to easily submit the identified epitopes to the lEDB, as we have already accomplished this task in the context of several previous epitope identiflcation projects.
The goal of this core is to identify the epitopes recognized by antigen-specific T cells that respond to zoster vaccine or infection. This will be a prelude to the analysis of epitope specific T cell responses to vaccination, and facilitate the identification of innate signatures that predict the breadth of the T cell response.
|Suthar, Mehul S; Pulendran, Bali (2014) Systems analysis of West Nile virus infection. Curr Opin Virol 6:70-5|
|Pulendran, Bali (2014) Systems vaccinology: probing humanity's diverse immune systems with vaccines. Proc Natl Acad Sci U S A 111:12300-6|
|Janssens, Sophie; Pulendran, Bali; Lambrecht, Bart N (2014) Emerging functions of the unfolded protein response in immunity. Nat Immunol 15:910-9|
|Tan, Yan; Tamayo, Pablo; Nakaya, Helder et al. (2014) Gene signatures related to B-cell proliferation predict influenza vaccine-induced antibody response. Eur J Immunol 44:285-95|
|Kwissa, Marcin; Nakaya, Helder I; Onlamoon, Nattawat et al. (2014) Dengue virus infection induces expansion of a CD14(+)CD16(+) monocyte population that stimulates plasmablast differentiation. Cell Host Microbe 16:115-27|
|Chiu, Christopher; McCausland, Megan; Sidney, John et al. (2014) Broadly reactive human CD8 T cells that recognize an epitope conserved between VZV, HSV and EBV. PLoS Pathog 10:e1004008|
|Cortese, Mario; Sinclair, Charles; Pulendran, Bali (2014) Translating glycolytic metabolism to innate immunity in dendritic cells. Cell Metab 19:737-9|
|Oh, Jason Z; Ravindran, Rajesh; Chassaing, Benoit et al. (2014) TLR5-mediated sensing of gut microbiota is necessary for antibody responses to seasonal influenza vaccination. Immunity 41:478-92|
|Yu, Tianwei; Jones, Dean P (2014) Improving peak detection in high-resolution LC/MS metabolomics data using preexisting knowledge and machine learning approach. Bioinformatics 30:2941-8|
|Ravindran, Rajesh; Khan, Nooruddin; Nakaya, Helder I et al. (2014) Vaccine activation of the nutrient sensor GCN2 in dendritic cells enhances antigen presentation. Science 343:313-7|
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