Antibodies Recognizing Mycobacterium avium paratuberculosis Epitopes Cross-React with the Beta-Cell Antigen ZnT8 in Sardinian Type 1 Diabetic Patients
(A) Aminoacid sequence alignment of ZnT8 (Slc30A8) and MAP3865c proteins. Conserved aminoacid residues are highlighted in yellow within the MAP3865c sequence and listed in bold below the two sequence alignment rows. The other color codes refer to the ZnT8 protein structure shown in (B): sequences highlighted in green belong to the 3 intra-luminal loops; the sequence in red belongs to the fourth transmembrane domain, while those in blue belong to the other transmembrane regions; sequences not highlighted fall within the 4 extra-luminal fragments. Dotted rectangles show the MAP3865c125–133/ZnT8178–186 and MAP3865c133–141/ZnT8186–194 peptides studied in subsequent experiments. The topology of the ZnT8 protein is also shown in panel (B), where the 3 intra-luminal loops (in green) become extracellularly exposed once the insulin granule is released. Conversely, the 4 extra-luminal domains (in black) are exposed to the cytosol and remain intracellular upon insulin exocytosis.