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- W2956965185 abstract "It is still an enigma why T cell autoreactivity in type 1 diabetes targets few beta cell antigens only. Among these, one primary autoantigen is pro(insulin). Autoimmune T cells preferentially recognise three epitopes on the proinsulin molecule, of which the peptide region B:11-23 is the dominant one. Interestingly, the three regions superimpose with binding sites of the chaperone hsp70, the region B:11-23 being the strongest binding one. Absence of an intact core region B:15-17 prevents autoimmune diabetes in NOD as well as binding of hsp70. A role of hsp70 in selecting autoimmune epitopes is supported by the ability of this and other chaperones to deliver bound peptides to MHC class I and II molecules for efficient antigen presentation. Binding of hsp70 to receptors on antigen presenting cells such as TLR4 results in costimulatory signals for T cell activation. Strongest effects are seen for the mixture of hsp70 with the peptide B:11-23. Thus, hsp70 may assist in proinsulin epitope selection and efficient presentation to autoreactive T cells. The concept of chaperone guided immune reactivity may also apply to other autoimmune diseases." @default.
- W2956965185 created "2019-07-23" @default.
- W2956965185 creator A5069424368 @default.
- W2956965185 creator A5090127748 @default.
- W2956965185 date "2019-12-01" @default.
- W2956965185 modified "2023-09-26" @default.
- W2956965185 title "Chaperones may cause the focus of diabetes autoimmunity on distinct (pro)insulin peptides" @default.
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- W2956965185 doi "https://doi.org/10.1016/j.jaut.2019.102304" @default.
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