T‐cell immunity against Severe Acute Respiratory Syndrome Coronavirus 2 proteins in patients with type 1 diabetes

Aims Individuals with type 1 diabetes (T1D) do not appear to have an elevated risk of severe Coronavirus Disease 19 (COVID‐19). Pre‐existing immune reactivity to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) in unexposed individuals may serve as a protective factor. Hence, our study was designed to evaluate the existence of T cells with reactivity against SARS‐CoV‐2 antigens in unexposed patients with T1D. Materials and methods Peripheral blood mononuclear cells (PBMCs) were collected from SARS‐CoV‐2 unexposed patients with T1D and healthy control subjects. SARS‐CoV‐2 specific T cells were identified in PBMCs by ex‐vivo interferon (IFN)γ‐ELISpot and flow cytometric assays. The epitope specificity of T cells in T1D was inferred through T Cell Receptor sequencing and GLIPH2 clustering analysis. Results T1D patients unexposed to SARS‐CoV‐2 exhibited higher rates of virus‐specific T cells than controls. The T cells primarily responded to peptides from the ORF7/8, ORF3a, and nucleocapsid proteins. Nucleocapsid peptides predominantly indicated a CD4+ response, whereas ORF3a and ORF7/8 peptides elicited both CD4+ and CD8+ responses. The GLIPH2 clustering analysis of TCRβ sequences suggested that TCRβ clusters, associated with the autoantigens proinsulin and Zinc transporter 8 (ZnT‐8), might share specificity towards ORF7b and ORF3a viral epitopes. Notably, PBMCs from three T1D patients exhibited T cell reactivity against both ORF7b/ORF3a viral epitopes and proinsulin/ZnT‐8 autoantigens. Conclusions The increased frequency of SAR‐CoV‐2‐ reactive T cells in T1D patients might protect against severe COVID‐19 and overt infections. These results emphasise the long‐standing association between viral infections and T1D.