insight regarding the role of PTPN22 (R620W) risk allele in regulation of signal transduction and maintenance of immune tolerance. Interestingly, when the analog mutation of (R620W) has been knocked into the murine ortholog of the gene, this mutation did not influence the half-life of PTPN22 protein as previously suggested [54] but altered receptor-mediated protein tyrosine phosphorylation and caused hypersensitivity to antigen receptor stimulation. Indeed, B cell expression of the risk variant was sufficient to promote systemic autoimmunity [55], [56].
