Antigenic mimicry between HLA and retinal autoantigen: a clue for pathogenesis and therapy of uveitis

Autoimmune uveitis is an inflammatory disease of the inner eye, which impairs vision and sometimes even leads to blindness. Due to the immune privilege of the eye, initiation of an autoaggressive immune response to ocular autoantigens was hard to explain. We could describe antigenic mimicry between a peptide derived from an ocular autoantigen and a peptide from the sequence of disease associated HLA-antigens. This mimicry can explain 1) the peripheral initiation of an autoaggressive immune response directed against sequestered ocular antigens and 2) the associations of HLA-class I antigens with a disease mediated by CD4(+) T cells. After demonstrating uveitogenicity and tolerogenicity of this HLA-peptide in the rat model of uveitis, we initiated a therapeutic trial for uveitis patients by oral tolerance induction with the HLA-peptide.