Tolerance checkpoint bypass permits emergence of pathogenic T cells to neuromyelitis optica autoantigen aquaporin-4.

ABSTRACT: Aquaporin-4 (AQP4)-specific T cells are expanded in neuromyelitis optica (NMO) patients and exhibit Th17 polarization. However, their pathogenic role in CNS autoimmune inflammatory disease is unclear. Although multiple AQP4 T-cell epitopes have been identified in WT C57BL/6 mice, we observed that neither immunization with those determinants nor transfer of donor T cells targeting them caused CNS autoimmune disease in recipient mice. In contrast, robust proliferation was observed following immunization of AQP4-deficient (AQP4^-/-) mice with AQP4 peptide (p) 135-153 or p201-220, peptides predicted to contain I-A^b-restricted T-cell epitopes but not identified in WT mice. In comparison with WT mice, AQP4^-/- mice used unique T-cell receptor repertoires for recogn

SUBMITTER: Sagan SA 

PROVIDER: S-EPMC5187685 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature