The autoimmune-predisposing variant of lymphoid tyrosine phosphatase favors T helper 1 responses.

ABSTRACT: The C1858T single nucleotide polymorphism in PTPN22, which is the gene encoding lymphoid tyrosine phosphatase (LYP), confers increased risk for various autoimmune disorders in Caucasians. Although the disease-associated LYP allele (LYP*W620) is a gain-of-function variant that has higher catalytic activity than the major allele (LYP*R620), it is still unclear how LYP*W620 predisposes for autoimmunity. Here, we compared both T cell signaling and T cell function in healthy human donors homozygous for either LYP*R620 or LYP*W620. Generally, the presence of LYP*W620 caused reduced proximal T cell antigen receptor-mediated signaling (e.g. ζ chain phosphorylation) but augmented CD28-associated signaling (e.g. AKT activation). Altered ligand binding properties of the two LYP variants could explain

SUBMITTER: Vang T 

PROVIDER: S-EPMC4011173 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature