DOI: 10.5061/dryad.msbcc2g55
title: Autoimmunity-associated allele of tyrosine phosphatase gene PTPN22 enhances anti-viral immunity

description: The 1858C&gt;T allele of the tyrosine phosphatase PTPN22 is present in
 5-10% of the North American population and is strongly associated with
 numerous autoimmune diseases. Although research has been done to define
 how this allele potentiates autoimmunity, the influence PTPN22 and its
 pro-autoimmune allele have in anti-viral immunity remains poorly defined.
 Here, we use single-cell RNA-sequencing and functional studies to
 interrogate the impact of this pro-autoimmune allele on anti-viral
 immunity during Lymphocytic Choriomeningitis Virus clone 13 (LCMV-cl13)
 infection. Mice homozygous for this allele (PEP-619WW) clear the LCMV-cl13
 virus whereas wildtype (PEP-WT) mice cannot. This is associated with
 enhanced anti-viral CD4 T cell responses and a more immunostimulatory
 CD8a- cDC phenotype. Adoptive transfer studies demonstrated that PEP-619WW
 enhanced anti-viral CD4 T cell function through virus-specific CD4 T
 cell-intrinsic and extrinsic mechanisms. Taken together, our data show
 that the pro-autoimmune allele of Ptpn22 drives a beneficial anti-viral
 immune response thereby preventing what is normally a chronic virus
 infection.
description: # Autoimmunity-associated allele of tyrosine phosphatase gene PTPN22
 enhances anti-viral immunity These data demonstrate the mice expressing
 the autoimmunity-associated allele of PTPN22 (PEP-619WW) have improved
 clearance of LCMV-clone 13 and this is associated with an enhanced immune
 response in numerous immune cell types. This was shown through single-cell
 RNA sequencing, infection disease course studies, and functional analysis
 using adoptive transfers and flow cytometry. The Prism file contains
 information on all the raw data tables, statistical analysis, and the
 resulting graphs. There are 55 data tables. ## Description of the data and
 file structure The dataset contains raw data values, in Prism, for
 experiments listed in the publication. These datasets include weight loss
 values and survival for LCMV-clone13 infection studies, organ LCMV-clone13
 titer data, and numerous files on quantifying different immune cell types,
 phenotypes, and functions derived from flow cytometry. Each data set file
 and graph file is labeled with a description of the experiment and
 correlates with the data presented in the manuscript. Analyses for each
 data set are also included. Single-cell RNA sequence raw data is not
 included in the dataset and is part of the GEO accession referenced in the
 manuscript. * Ptpn22 1858C&gt;T expressing mice labeled as PEP-619WW or
 PEP-WW or PEP-R619W * Ptpn22 wildtype mice labeled as PEP-WT * Ptpn22
 knockout mice labeled as PEP-null or KO * Abs. No. = Absolute Number * PEP
 = PEST-domain Enriched Phosphatase * LCMV-cl13 = Lymphocytic
 choriomeningitis virus clone 13 * Treg = T regulatory cell * Dpi = days
 post-infection * LCMV-NP = Lymphocytic choriomeningitis virus
 Nucleoprotein * cDC = conventional Dendritic Cell * pDC = plasmacytoid
 Dendritic Cell * IFN-I = Type I Interferon * Th1 = T Helper 1 cell * TFH =
 T Follicular helper cell * IFNg = Interferon-gamma * TNFa = Tumor necrosis
 factor-alpha * IL-2 = Interleukin 2 * GP = glycoprotein * PD-L1 = Program
 death receptor ligand 1 * APC = antigen-presenting cell ## Sharing/Access
 information NA ## Code/Software NA