Autoimmune Risk, Antiviral Reward: Defining Impacts of PTPN22’s Disease-Associated Allele on Antiviral Immunity 4347

Abstract Description Genetic factors contributing to both disease and immune resilience present a scientific conundrum. PTPN22, a phosphatase-encoding gene that regulates T and B cell signaling, highlights this duality with its autoimmunity-associated allele (PEP-R619W in mice). Previously, studies have shown PEP-R619W mice can clear Lymphocytic Choriomeningitis Virus clone 13 (LCMV-cl13) whereas PEP-WT cannot. This has, in part, been attributed to increased dendritic cell antigen presentation and T cell function. However, there is also an increase in IgG2A antibodies present in serum at 9 days post infection (DPI). Currently, the explicit role of PEP-R619W in B cells during virus infection, both in antibody production and as an antigen presenting cell (APC), remains largely unknown. We hypothesize PEP-R619W enhances antiviral immunity via IgG2A production and B cell-mediated CD4 T cell activation. To test our hypothesis, we first developed a neutralization assay, showing PEP-R619W serum reduces LCMV infection. Then, to test B cell-mediated CD4 T cell activation, we co-cultured B cells with LCMV-specific CD4 T cells and stained for activation-specific markers, quantified by flow cytometry. Preliminary coculture data suggests PEP-R619W B cells increase PEP-WT CD4 T cell activation. Together, these findings shed light on PTPN22’s impacts on neutralizing antibodies and APC function, providing a foundation to leverage its benefits towards targeted, antiviral immunotherapies. Funding Sources Supported by CBID CoBRE Research Grant (KU)-P20GM113117; KU Postbaccalaureate Research Education Program Topic Categories Viral Immunology (VIR)