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@ARTICLE{Azoury:176904,
      author       = {M. E. Azoury and F. Samassa and M. Buitinga and L. Nigi and
                      N. Brusco and A. Callebaut and M. Giraud and M. Irla and A.
                      I. Lalanne and A. Carré and G. Afonso and Z. Zhou and B.
                      Brandao and M. L. Colli and G. Sebastiani and F. Dotta and
                      M. Nakayama and D. L. Eizirik and S. You and S. Pinto$^*$
                      and M. J. Mamula and Y. Verdier and J. Vinh and S. Buus and
                      C. Mathieu and L. Overbergh and R. Mallone},
      title        = {{CD}8+ {T} cells variably recognize native versus
                      citrullinated {GRP}78 epitopes in type 1 diabetes.},
      journal      = {Diabetes},
      volume       = {70},
      number       = {12},
      issn         = {1939-327X},
      address      = {Alexandria, Va},
      publisher    = {Assoc.},
      reportid     = {DKFZ-2021-02146},
      pages        = {2879-2891},
      year         = {2021},
      note         = {Deutsches Krebsforschungszentrum (DKFZ), Division of
                      Developmental Immunology, 69120 Heidelberg, Germany., 2021
                      Dec;70(12):2879-2891},
      abstract     = {In type 1 diabetes, autoimmune β-cell destruction may be
                      favored by neo-antigens harboring post-translational
                      modifications such as citrullination. We studied the
                      recognition of native and citrullinated glucose-regulated
                      protein (GRP)78 peptides by CD8+ T cells. Citrullination
                      modulated T-cell recognition and, to a lesser extent, HLA-A2
                      binding. GRP78-reactive CD8+ T cells circulated at similar
                      frequencies in type 1 diabetic and healthy donors and
                      preferentially recognized either native or citrullinated
                      versions, without cross-reactivity. Rather, the preference
                      for native GRP78 epitopes was associated with CD8+ T cells
                      cross-reactive with bacterial mimotopes. In the pancreas, a
                      dominant GRP78 peptide was instead preferentially recognized
                      when citrullinated. To further clarify these recognition
                      patterns, we considered the possibility of citrullination in
                      the thymus. Citrullinating peptidyl-arginine deiminase
                      (Padi) enzymes were expressed in murine and human medullary
                      epithelial cells (mTECs), with citrullinated proteins
                      detected in murine mTECs. However, Padi2 and Padi4
                      expression was diminished in mature mTECs from NOD mice
                      versus C57BL/6 mice. We conclude that, on one hand, the CD8+
                      T-cell preference for native GRP78 peptides may be shaped by
                      cross-reactivity with bacterial mimotopes. On the other
                      hand, post-translational modifications may not invariably
                      favor loss of tolerance because thymic citrullination,
                      although impaired in NOD mice, may drive deletion of
                      citrulline-reactive T cells.},
      cin          = {D090 ; D090},
      ddc          = {610},
      cid          = {I:(DE-He78)D090-20160331},
      pnm          = {314 - Immunologie und Krebs (POF4-314)},
      pid          = {G:(DE-HGF)POF4-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34561224},
      doi          = {10.2337/db21-0259},
      url          = {https://inrepo02.dkfz.de/record/176904},
}