Journal Article

DKFZ-2021-02146

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png CD8+ T cells variably recognize native versus citrullinated GRP78 epitopes in type 1 diabetes.

Azoury, M. E. ; Samassa, F. ; Buitinga, M. ; Nigi, L. ; Brusco, N. ; Callebaut, A. ; Giraud, M. ; Irla, M. ; Lalanne, A. I. ; Carré, A. ; Afonso, G. ; Zhou, Z. ; Brandao, B. ; Colli, M. L. ; Sebastiani, G. ; Dotta, F. ; Nakayama, M. ; Eizirik, D. L. ; You, S. ; Pinto, S.DKFZ* ; Mamula, M. J. ; Verdier, Y. ; Vinh, J. ; Buus, S. ; Mathieu, C. ; Overbergh, L. ; Mallone, R.

2021
Assoc. Alexandria, Va

This record in other databases:  

Please use a persistent id in citations: doi:10.2337/db21-0259

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.

Note: Deutsches Krebsforschungszentrum (DKFZ), Division of Developmental Immunology, 69120 Heidelberg, Germany., 2021 Dec;70(12):2879-2891

---

Contributing Institute(s):

1. Entwicklungsimmunologie (D090 ; D090)

Research Program(s):

1. 314 - Immunologie und Krebs (POF4-314) (POF4-314)

Appears in the scientific report 2021

---

Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---