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Structural mechanism of B‐ and T‐cell immune responses mediated by IDDM autoantigen IA‐2
Author(s) -
Ryu Seong Eon,
Kim Seung Jun,
Jeong Dae Gwin,
Jeong Sook Kyung,
Yoon TaeSung
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.227
Subject(s) - epitope , protein tyrosine phosphatase , immune system , mutagenesis , t cell , chemistry , mechanism (biology) , protein structure , biology , microbiology and biotechnology , tyrosine , antibody , immunology , biochemistry , mutation , philosophy , gene , epistemology
IA‐2 is a major autoantigen in the type‐I diabetes that occurs through the autoimmune‐mediated β‐cell destruction. We present here the crystal structure of the protein tyrosine phosphatase (PTP)‐like domain of human IA‐2. The structure reveals a canonical PTP domain with the closed WPD loop over the active site pocket, explaining the lack of enzyme activity in the native protein. The structural interpretation of previous mutagenesis studies indicates that the B‐cell epitopes are concentrated on two distinctive regions on peripheral loops of the central β‐sheet surrounding T‐cell epitopes within the sheet. The detailed structural information on immune epitopes provides a framework for the future development of immune intervention strategies against diabetes.