Human Aquaporin 4_281-300Is the Immunodominant Linear Determinant in the Context of HLA-DRB1*03:01

A Single Amino Acid Substitution Prevents Recognition of a Dominant Human Aquaporin-4 Determinant in the Context of HLA-DRB1*03:01 by a Murine TCR

“…Thus, B cells of HLA-DRB1*03 : 01 transgenic mice are capable of recognizing hAQP4 281-300 peptide via the B cell receptor (BCR), and the cellular immune response against hAQP4 281-300 subsequently drives Ig isotype switching. These data support our previously published data that hAQP4 281-300 is a dominant determinant in HLA-DRB1*03:01 [ 21 ] .…”

“…A multitude of experimental procedures and conditions were tested to examine the encephalitogenic potential of hAQP4 peptides using the transgenic mice. Previously, our laboratory determined that hAQP4 281-300 was capable of generating a strong Th 1 and Th 17 immune response as measured by IFNγ and IL-17 ELISpot assay [ 21 ]. We performed active immunization with whole-length hAQP4 protein, hAQP4 281-300 , or mAQP4 281-300 in an attempt to generate an animal model of NMO.…”

“…To identify critical residues of the AQP4 peptides, alanine-scanning peptides were generated that replaced each amino acid of mAQP4 281-300 with an alanine to aid in distinguishing anchor residues from contact residues ( Table 1 ). Since we previously identified hAQP4 284-299 to be the immunogenic region within hAQP4 281-299 [ 21 ], the alanine scanning peptides assessed only these residues.…”

A Single Amino Acid Substitution Prevents Recognition of a Dominant Human Aquaporin-4 Determinant in the Context of HLA-DRB1*03:01 by a Murine TCR

“…Thus, B cells of HLA-DRB1*03 : 01 transgenic mice are capable of recognizing hAQP4 281-300 peptide via the B cell receptor (BCR), and the cellular immune response against hAQP4 281-300 subsequently drives Ig isotype switching. These data support our previously published data that hAQP4 281-300 is a dominant determinant in HLA-DRB1*03:01 [ 21 ] .…”

“…A multitude of experimental procedures and conditions were tested to examine the encephalitogenic potential of hAQP4 peptides using the transgenic mice. Previously, our laboratory determined that hAQP4 281-300 was capable of generating a strong Th 1 and Th 17 immune response as measured by IFNγ and IL-17 ELISpot assay [ 21 ]. We performed active immunization with whole-length hAQP4 protein, hAQP4 281-300 , or mAQP4 281-300 in an attempt to generate an animal model of NMO.…”

“…To identify critical residues of the AQP4 peptides, alanine-scanning peptides were generated that replaced each amino acid of mAQP4 281-300 with an alanine to aid in distinguishing anchor residues from contact residues ( Table 1 ). Since we previously identified hAQP4 284-299 to be the immunogenic region within hAQP4 281-299 [ 21 ], the alanine scanning peptides assessed only these residues.…”

Immune tolerance in multiple sclerosis and neuromyelitis optica with peptide-loaded tolerogenic dendritic cells in a phase 1b trial

“…As such, the T-cell immunogenic peptide AQP4 63–76 described by Zamvil and coworkers (23) was used in this trial, because it was the only known human disease-related epitope when we started the trial. New AQP4 epitopes have been described (44, 45), which would be tested in future trials.…”

Deletional tolerance prevents AQP4‐directed autoimmunity in mice

“…Although the authors of that study suggested that AQP4 (61-80) is a naturally processed determinant of AQP4, it is unclear whether AQP4(61-80)-specific T cells contribute to the formation of anti-AQP4 antibodies. Furthermore, T-cell epitopes of AQP4 have been reported in rats [39], mice [23,40,41], and humanized DRB1*0301 transgenic mice [42], but none of them has been confirmed to be a naturally processed epitope since active immunization has never been reported to induce clinical signs of disease in any of these models. Besides AQP4(201-220), a further IA b -restricted epitope of AQP4, i.e.…”

A Single Amino Acid Substitution Prevents Recognition of a Dominant Human Aquaporin-4 Determinant in the Context of HLA-DRB1*03:01 by a Murine TCR

“…Thus, B cells of HLA-DRB1*03 : 01 transgenic mice are capable of recognizing hAQP4 281-300 peptide via the B cell receptor (BCR), and the cellular immune response against hAQP4 281-300 subsequently drives Ig isotype switching. These data support our previously published data that hAQP4 281-300 is a dominant determinant in HLA-DRB1*03:01 [ 21 ] .…”

“…A multitude of experimental procedures and conditions were tested to examine the encephalitogenic potential of hAQP4 peptides using the transgenic mice. Previously, our laboratory determined that hAQP4 281-300 was capable of generating a strong Th 1 and Th 17 immune response as measured by IFNγ and IL-17 ELISpot assay [ 21 ]. We performed active immunization with whole-length hAQP4 protein, hAQP4 281-300 , or mAQP4 281-300 in an attempt to generate an animal model of NMO.…”

“…To identify critical residues of the AQP4 peptides, alanine-scanning peptides were generated that replaced each amino acid of mAQP4 281-300 with an alanine to aid in distinguishing anchor residues from contact residues ( Table 1 ). Since we previously identified hAQP4 284-299 to be the immunogenic region within hAQP4 281-299 [ 21 ], the alanine scanning peptides assessed only these residues.…”

Immune tolerance in multiple sclerosis and neuromyelitis optica with peptide-loaded tolerogenic dendritic cells in a phase 1b trial

“…As such, the T-cell immunogenic peptide AQP4 63–76 described by Zamvil and coworkers (23) was used in this trial, because it was the only known human disease-related epitope when we started the trial. New AQP4 epitopes have been described (44, 45), which would be tested in future trials.…”

Deletional tolerance prevents AQP4‐directed autoimmunity in mice

“…Although the authors of that study suggested that AQP4 (61-80) is a naturally processed determinant of AQP4, it is unclear whether AQP4(61-80)-specific T cells contribute to the formation of anti-AQP4 antibodies. Furthermore, T-cell epitopes of AQP4 have been reported in rats [39], mice [23,40,41], and humanized DRB1*0301 transgenic mice [42], but none of them has been confirmed to be a naturally processed epitope since active immunization has never been reported to induce clinical signs of disease in any of these models. Besides AQP4(201-220), a further IA b -restricted epitope of AQP4, i.e.…”

A Single Amino Acid Substitution Prevents Recognition of a Dominant Human Aquaporin-4 Determinant in the Context of HLA-DRB1*03:01 by a Murine TCR

“…Thus, B cells of HLA-DRB1*03 : 01 transgenic mice are capable of recognizing hAQP4 281-300 peptide via the B cell receptor (BCR), and the cellular immune response against hAQP4 281-300 subsequently drives Ig isotype switching. These data support our previously published data that hAQP4 281-300 is a dominant determinant in HLA-DRB1*03:01 [ 21 ] .…”

“…A multitude of experimental procedures and conditions were tested to examine the encephalitogenic potential of hAQP4 peptides using the transgenic mice. Previously, our laboratory determined that hAQP4 281-300 was capable of generating a strong Th 1 and Th 17 immune response as measured by IFNγ and IL-17 ELISpot assay [ 21 ]. We performed active immunization with whole-length hAQP4 protein, hAQP4 281-300 , or mAQP4 281-300 in an attempt to generate an animal model of NMO.…”

“…To identify critical residues of the AQP4 peptides, alanine-scanning peptides were generated that replaced each amino acid of mAQP4 281-300 with an alanine to aid in distinguishing anchor residues from contact residues ( Table 1 ). Since we previously identified hAQP4 284-299 to be the immunogenic region within hAQP4 281-299 [ 21 ], the alanine scanning peptides assessed only these residues.…”

Immune tolerance in multiple sclerosis and neuromyelitis optica with peptide-loaded tolerogenic dendritic cells in a phase 1b trial

“…As such, the T-cell immunogenic peptide AQP4 63–76 described by Zamvil and coworkers (23) was used in this trial, because it was the only known human disease-related epitope when we started the trial. New AQP4 epitopes have been described (44, 45), which would be tested in future trials.…”

Deletional tolerance prevents AQP4‐directed autoimmunity in mice

“…Although the authors of that study suggested that AQP4 (61-80) is a naturally processed determinant of AQP4, it is unclear whether AQP4(61-80)-specific T cells contribute to the formation of anti-AQP4 antibodies. Furthermore, T-cell epitopes of AQP4 have been reported in rats [39], mice [23,40,41], and humanized DRB1*0301 transgenic mice [42], but none of them has been confirmed to be a naturally processed epitope since active immunization has never been reported to induce clinical signs of disease in any of these models. Besides AQP4(201-220), a further IA b -restricted epitope of AQP4, i.e.…”