One typical autoimmunity danger variant– an anomaly that switches an arginine to a tryptophan (R620W) in the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene– associates with various autoimmune conditions and almost doubles a persons danger of type 1 diabetes, systemic lupus erythematosus, and rheumatoid arthritis.1 PTPN22 is extremely expressed in lymphocytes where it affects T cell receptor (TCR) signaling and T cell activation. While PTPN22 R620W is well known, it is not well comprehended, leading to opposing opinions about the versions effects.2 When a T cell receptor (TCR) binds its target antigen, a signaling waterfall starts within the cell, driving its expansion and activation. PTPN22 negatively regulates this response by dephosphorylating key proteins in the pathway.3 The R620W mutation keeps PTPN22 from making it to the membrane where the proteins it communicates with live.4 To determine the more comprehensive consequences of this mislocalization, scientists genetically engineered this variant into mice and discovered an increase in T cell signaling and activation. Previously, scientists discovered that PTPN22 repressed T cell activation by antigens that weakly bound to the TCR.6 Rawlings believed that the R620W mutation may enhance autoimmunity by activating T cells with low-avidity TCRs that acknowledged self antigens. PTPN22 R620W gene editing in T cells boosts low-avidity TCR reactions.
One typical autoimmunity threat version– an anomaly that changes an arginine to a tryptophan (R620W) in the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene– associates with many autoimmune conditions and nearly doubles a persons danger of type 1 diabetes, systemic lupus erythematosus, and rheumatoid arthritis.1 PTPN22 is highly expressed in lymphocytes where it affects T cell receptor (TCR) signaling and T cell activation. While PTPN22 R620W is well understood, it is not well understood, leading to opposing viewpoints about the variations consequences.2 When a T cell receptor (TCR) binds its target antigen, a signaling cascade initiates within the cell, driving its proliferation and activation. Formerly, researchers discovered that PTPN22 quelched T cell activation by antigens that weakly bound to the TCR.6 Rawlings thought that the R620W mutation might enhance autoimmunity by activating T cells with low-avidity TCRs that recognized self antigens.
