Epitopes described in "Immunodominant T cell determinants of aquaporin-4, the autoantigen associated with neuromyelitis optica."

Article Authors:Patricia A Nelson; Mojgan Khodadoust; Thomas Prodhomme; Collin Spencer; Juan Carlos Patarroyo; Michel Varrin-Doyer; Joseph D Ho; Robert M Stroud; Scott S Zamvil
Article Title:Immunodominant T cell determinants of aquaporin-4, the autoantigen associated with neuromyelitis optica.
Reference Detail
Reference ID:1021154
Abstract:Autoantibodies that target the water channel aquaporin-4 (AQP4) in neuromyelitis optica (NMO) are IgG1, a T cell-dependent Ig subclass. However, a role for AQP4-specific T cells in this CNS inflammatory disease is not known. To evaluate their potential role in CNS autoimmunity, we have identified and characterized T cells that respond to AQP4 in C57BL/6 and SJL/J mice, two strains that are commonly studied in models of CNS inflammatory diseases. Mice were immunized with either overlapping peptides or intact hAQP4 protein encompassing the entire 323 amino acid sequence. T cell determinants identified from examination of the AQP4 peptide (p) library were located within AQP4 p21-40, p91-110, p101-120, p166-180, p231-250 and p261-280 in C57BL/6 mice, and within p11-30, p21-40, p101-120, p126-140 and p261-280 in SJL/J mice. AQP4-specific T cells were CD4+ and MHC II-restricted. In recall responses to immunization with intact AQP4, T cells responded primarily to p21-40, indicating this region contains the immunodominant T cell epitope(s) for both strains. AQP4 p21-40-primed T cells secreted both IFN- and IL-17. The core immunodominant AQP4 21-40 T cell determinant was mapped to residues 24-35 in C57BL/6 mice and 23-35 in SJL/J mice. Our identification of the AQP4 T cell determinants and characterization of its immunodominant determinant should permit investigators to evaluate the role of AQP4-specific T cells in vivo and to develop AQP4-targeted murine NMO models.
Reference Type:Literature
PubMed ID:21151500
Journal:PLoS One
Journal Volume:5
Article Pages:e15050
Journal ISSN:1932-6203
Article Chemical List:Aquaporin 4;Autoantibodies;Autoantigens;Epitopes, T-Lymphocyte;Immunodominant Epitopes;Interleukin-17;Peptides;Interferon-gamma
Article MeSH List:Amino Acid Sequence; Animals; Aquaporin 4(immunology); Autoantibodies(immunology); Autoantigens(immunology); CD4-Positive T-Lymphocytes(immunology; metabolism); Enzyme-Linked Immunosorbent Assay; Epitope Mapping; Epitopes, T-Lymphocyte(chemistry; immunology); Humans; Immunization; Immunodominant Epitopes(chemistry; immunology); Interferon-gamma(immunology; metabolism); Interleukin-17(immunology; metabolism); Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Molecular Sequence Data; Neuromyelitis Optica(diagnosis; immunology); Peptides(chemistry; immunology)
Curation Last Updated:2015-12-11 20:12:05