RT Journal Article
T1 Naturally presented HLA class I–restricted epitopes from the neurotrophic factor S100-β are targets of the autoimmune response in type 1 diabetes
A1 Calviño Sampedro, Cristina
A1 Gómez Touriño, Iria María
A1 Cordero Santamaría, Óscar Javier
A1 Reche Gallardo, Pedro Antonio
A1 Gómez Perosanz, Marta
A1 Rodríguez Díaz, Miguel Ángel
A1 Sueiro, Aurelio M.
A1 Viñuela Roldán, Juan Evaristo
A1 Varela Calviño, Rubén
K1 Cytotoxic lymphocytes
K1 Autoantigen
K1 S100b peptide epitopes
K1 Immunotherapy
K1 Peri-insular Schwann cells
AB Type 1 diabetes (T1D) results from the destruction of pancreatic β-cells by the immune system, and CD8+ T lymphocytes are critical actors in this autoimmune response. Pancreatic islets are surrounded by a mesh of nervous cells, the peri-insular Schwann cells, which are also targeted by autoreactive T lymphocytes and express specific antigens, such as the neurotrophic factor S100-β. Previous work has shown increased proliferative responses to whole S100-β in both human T1D patients and the nonobese diabetic (NOD) mouse model. We describe for the first time naturally processed and presented epitopes (NPPEs) presented by class I human leukocyte antigen–A*02:01 (A2.1) molecules derived from S100-β. These NPPEs triggered IFN-γ responses more frequently in both newly diagnosed and long-term T1D patients compared with healthy donors. Furthermore, the same NPPEs are recognized during the autoimmune response leading to diabetes in A2.1-transgenic NOD mice as early as 4 wk of age. Interestingly, when these NPPEs are used to prevent diabetes in this animal model, an acceleration of the disease is observed together with an exacerbation in insulitis and an increase in S100-β–specific cytotoxicity in vaccinated animals. Whether these can be used in diabetes prevention needs to be carefully evaluated in animal models before use in future clinical assays.—Calviño-Sampedro, C., Gomez-Tourino, I., Cordero, O. J., Reche, P. A., Gómez-Perosanz, M., Sánchez-Trincado, J. L., Rodríguez, M. Á., Sueiro, A. M., Viñuela, J. E., Calviño, R. V. Naturally presented HLA class I–restricted epitopes from the neurotrophic factor S100-β are targets of the autoimmune response in type 1 diabetes
PB Federation of American Societies for Experimental Biology
SN 0892-6638
YR 2019
FD 2019
LK http://hdl.handle.net/10347/18515
UL http://hdl.handle.net/10347/18515
LA eng
NO Calviño-Sampedro, C., Gomez-Tourino, I., Cordero, O., Reche, P., Gómez-Perosanz, M., & Sánchez-Trincado, J. et al. (2019). Naturally presented HLA class I–restricted epitopes from the neurotrophic factor S100-β are targets of the autoimmune response in type 1 diabetes. The FASEB Journal, fj.201802270R. doi: 10.1096/fj.201802270r
NO The authors thank Dr. Sefina Arif (King’s College London,London, United Kingdom) for critically reviewing the manuscript.This work was funded by the Ministerio de Economía yCompetitividad (Grant BIO2014-53091-C3-3-R to R.V.C.). Duringthis work, I.G.-T. was supported by a Maria Barbeito predoctoralfellowship (Xunta de Galicia, La Coruña, Spain). During thiswork, C.C.-S. was supported by a Deputación da Coruña grant(2012–2013 and 2016–2017)
DS Minerva
RD 24 abr 2026