functional characterization of aquaporin-4 specific t cells towards a model for neuromyelitis optica功能描述aquaporin-4特异性t细胞对视神经节neuromyelitis的典范.pdfVIP

Functional Characterization of Aquaporin-4 Specific T Cells: Towards a Model for Neuromyelitis Optica 1 1 2 1 Sudhakar Reddy Kalluri , Veit Rothhammer , Ori Staszewski , Rajneesh Srivastava , Franziska 1 2 1 1 Petermann , Marco Prinz , Bernhard Hemmer , Thomas Korn * ¨ ¨ ¨ 1 Department of Neurology, Klinikum rechts der Isar, Technische Universitat Munchen, Munchen, Germany, 2 Department of Neuropathology, Institute of Pathology, ¨ Universitatsklinikum Freiburg, Freiburg, Germany Abstract Background: Antibodies to the water channel protein aquaporin-4 (AQP4), which is expressed in astrocytic endfeet at the blood brain barrier, have been identified in the serum of Neuromyelitis optica (NMO) patients and are believed to induce damage to astrocytes. However, AQP4 specific T helper cell responses that are required for the generation of anti-AQP4 antibodies and most likely also for the formation of intraparenchymal CNS lesions have not been characterized. Methodology/Principal Findings: Using overlapping 15-meric peptides of AQP4, we identified the immunogenic T cell epitopes of AQP4 that are restricted to murine major histocompatibility complex (MHC) I-Ab. The N-terminal region of AQP4 was highly immunogenic. More precisely, the intracellular epitope AQP422–36 was detected as major immunogenic determinant. AQP482–108 (located in the second transmembrane domain), AQP4139–153 (located in the second extracellular loop), AQP4211–225 (located in the fifth transmembrane domain), AQP4235–249 (located in the