This week Science published intriguing study showing that in type I diabetic individuals hybrid peptides derived from two unrelated proteins represent novel auto-antigens.
Initially, the authors showed that chemically cross-linked or synthetic peptide that is made one half of proinsulin C-peptide and another half from chromogranin A (ChgA) peptide (both β cell proteins), could activate diabetogenic mouse T cell clones.
Next, the authors showed that T cells specific for such hybrid peptides can be detected in un-manipulated diabetes susceptible NOD female mice (it would have been more informative if the authors have included data from non-susceptible WT mice as a control).
Finally, the authors showed in T cells from T1D individuals could also recognize hybrid peptide made of human proinsulin C-peptide and neuropeptide Y.
In summary, this study suggests that in T1D susceptible individuals, diabetogenic auto-antigens could be generated by fusion of peptide derived from two unrelated proteins (a side reaction of the proteolytic hydrolysis of peptide in secretory granules). Whether generation of such immunogenic hybrid peptides happens only T1D susceptible individuals remains to be determined.
David Usharauli
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