Enabling epitope-resolved analysis of the CD4 T cell response to Valley fever at unprecedented breadth and resolution
Valley fever (Vf), caused by Coccidioides spp., is a fungal respiratory infection endemic to the southwestern United States. There are an estimated 350,000 cases reported nationally each year. The human T cell response plays a critical role in the defense against Vf by recognizing the pathogen, clearing the infection, and preventing re-infection. Although there are known Vf antigens that elicit this protective T cell response, the specific epitopes (regions of the antigen that are recognized by the T cell) are still unknown. The goal of this study is to identify novel T cell epitopes from Coccidioides antigens known to elicit a protective T cell response. In this project, PBMCs from Vf donors were isolated and HLA typed; the CD4+ T cell population was specifically expanded against 298 peptides representing eight Vf antigens. Antigen-specific T cell expansions were successful for seven of these; however, HLA typing is underway. Following HLA typing, we will begin construction of the HLA-peptide probeset for these donors. This probeset will be used for staining and single-cell sequencing. This will allow us to identify epitope-T cell receptor pairs, which informs the development of treatment options, e.g., vaccines or T cell-specific therapies, for patients with Valley fever.
