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Mishto, M.* ; Mansurkhodzhaev, A.* ; Rodriguez-Calvo, T. ; Liepe, J.*

Potential mimicry of viral and pancreatic β cell antigens through non-spliced and cis-spliced zwitter epitope candidates in type 1 diabetes.

Front. Immunol. 12:656451 (2021)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Increasing evidence suggests that post-translational peptide splicing can play a role in the immune response under pathological conditions. This seems to be particularly relevant in Type 1 Diabetes (T1D) since post-translationally spliced epitopes derived from T1D-associated antigens have been identified among those peptides bound to Human Leucocyte Antigen (HLA) class I and II complexes. Their immunogenicity has been confirmed through CD4 and CD8 T cell-mediated responses in T1D patients. Spliced peptides theoretically have a large sequence variability. This might increase the frequency of viral-human zwitter peptides, i.e. peptides that share a complete sequence homology irrespective of whether they originate from human or viral antigens, thereby impinging upon the discrimination between self and non-self antigens by T cells. This might increase the risk of autoimmune responses triggered by viral infections. Since enteroviruses and other viral infections have historically been associated with T1D, we investigated whether cis-spliced peptides derived from selected viruses might be able to trigger CD8 T cell-mediated autoimmunity. We computed in silico viral-human non-spliced and cis-spliced zwitter epitope candidates, and prioritized peptide candidates based on: (i) their binding affinity to HLA class I complexes, (ii) human pancreatic β cell and medullary thymic epithelial cell (mTEC) antigens’ mRNA expression, (iii) antigen association with T1D, and (iv) potential hotspot regions in those antigens. Neglecting potential T cell receptor (TCR) degeneracy, no viral-human zwitter non-spliced peptide was found to be an optimal candidate to trigger a virus-induced CD8 T cell response against human pancreatic β cells. Conversely, we identified some zwitter peptide candidates, which may be produced by proteasome-catalyzed peptide splicing, and might increase the likelihood of pancreatic β cells recognition by virus-specific CD8 T cell clones, therefore promoting β cell destruction in the context of viral infections. + + + + +
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Antigen Presentation ; Mimicry ; Spliced Peptides ; T1d ; Tolerance ; Virus
ISSN (print) / ISBN 1664-3224
e-ISSN 1664-3224
Zeitschrift Frontiers in Immunology
Quellenangaben Band: 12, Heft: , Seiten: , Artikelnummer: 656451 Supplement: ,
Verlag Frontiers
Verlagsort Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research Type 1 (IDF)
Förderungen MPI-BPC collaboration agreement 2020
European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme
Helmholtz Zentrum Munich
NIHR Clinical Research Facility
National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London
Cancer Research UK