Overexpression of HLA class I predominantly on alpha cell in at risk individuals for type 1 diabetes

Benkahla, M. A.; Sabouri, S.; Kiosses, W. B.; Rajendran, S.; Quesada-Masachs, E.; von Herrath, M. G.

doi:10.1101/2020.07.13.201079

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bioRxiv · 10.1101/2020.07.13.201079

Overexpression of HLA class I predominantly on alpha cell in at risk individuals for type 1 diabetes

Benkahla, M. A.·Sabouri, S.·Kiosses, W. B.·Rajendran, S.·Quesada-Masachs, E.·von Herrath, M. G.

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Abstract

Human leukocyte antigens of class-I (HLA-I) molecules are hyper-expressed in insulin-containing islets (ICI) of type 1 diabetic (T1D) donors. This study investigated the HLA-I expression in autoantibody positive (AAB+) donors and more closely defined its intra-islet and intracellular localization as well as proximity to infiltrating CD8 T cells with high-resolution confocal microscopy. We found HLA-I hyper-expression had already occurred prior to clinical diagnosis of T1D in islets of AAB+ donors. Interestingly, throughout all stages of disease, HLA-I was mostly expressed by alpha cells. Hyper-expression in AAB+ and T1D donors was associated with intra-cellular accumulation in the Golgi. Proximity analysis showed a moderate but significant correlation between HLA-I and infiltrating CD8 T cells only in ICI of T1D donors, but not in AAB+ donors. These observations not only demonstrate a very early, islet-intrinsic immune-independent increase of HLA-I during diabetes pathogenesis, but also point towards a role for alpha cells in T1D. SummaryHuman leukocyte antigens of class-I (HLA-I) are hyper-expressed in insulin-containing islets of type 1 diabetic (T1D) donors. This study finds HLA-I hyper-expression occurs prior to clinical diagnosis of T1D in islets of autoantibody-positive donors and mostly expressed by alpha cells.

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Benkahla, M. A., Sabouri, S., Kiosses, W. B., Rajendran, S., Quesada-Masachs, E., von Herrath, M. G.. 2020-07-14. Overexpression of HLA class I predominantly on alpha cell in at risk individuals for type 1 diabetes. https://doi.org/10.1101/2020.07.13.201079

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