Cross‐reactivity between an HLA‐B27‐derived peptide and a retinal autoantigen peptide: a clue to major histocompatibility complex association with autoimmune disease

Abstract

Statistical correlations between the expression of various HLA antigens and certain autoimmune diseases have been observed for both HLA class I and II antigens. Autoimmune diseases like spondyloarthropathies and anterior uveitis are associated with HLA-B27, but uveitis in Behçet's disease with HLA-B51. We describe a peptide from disease-associated HLA class I antigens sharing sequence homologies with a highly uveitogenic epitope from the retinal autoantigen S-antigen. S-antigen induces autoimmune uveitis in the animal model and is a major autoantigen in human disease. The HLA peptide induced uveitis in the Lewis rat and, moreover, suppressed S-antigen-induced disease when administered orally. Patients' PBL cross-reacted with the HLA- and corresponding retinal peptide, explaining the organ specificity of the disease.

Ocular involvement is associated with HLA-B51 in Adamantiades–Behçet's disease

“…31 One epitope of this protein is similar to HLA-B51 and -B27, the latter being another gene associated with uveitis. 32,33 It is likely that these proteins, once released, support and feed chronic uveitis. This might be an explanation why HLA-B51 is found in patients with ocular involvement.…”

HLA‐B27‐derived peptides as autoantigens for T lymphocytes in ankylosing spondylitis

“…B27PD has previously been demonstrated to be uveitogenic in the rat model of experimental autoimmune uveitis (EAU) (12). Peptide B7PD represents the sequence of some HLA-B antigens including HLA-B7, which differ from peptide B27PD by a single amino acid exchange, and was used as a control (Table 1).…”

“…Thus, peptides derived from the HLA-B27 a chain, probably mimicking epitopes of organ-specific autoantigens, may become candidate autoantigens in the development of AS or related spondylarthropathies. That mechanism has previously been described for autoimmune uveitis, another HLA class I-associated disease (12). In this study, we examined several synthetic peptides derived from the HLA-B27 hypervariable chain.…”

Pathogenesis of spondylarthropathies

“…In this context, 2 recent reports are of interest: 1 study demonstrated that B27 peptides show the highest homology of all class I MHC molecules to gram-negative enteric bacteria (66), and the other showed that the 2-Md plasmid of Shigella, which shows some homology with HLA-B27, was present only in arthritogenic, and not in nonarthritogenic, shigellae (67). Support for a crucial role of B27-derived peptides in the pathogenesis of spondylarthropathy comes also from a study showing reactivity of peripheral blood mononuclear cells to a B27 peptide in patients with HLA-B27-associated uveitis (a disease related to spondylarthropathy) but not in controls (68). Furthermore, in an animal model of experimental uveitis, oral tolerance could be induced by feeding the animals the same B27 peptide (68).…”

“…Support for a crucial role of B27-derived peptides in the pathogenesis of spondylarthropathy comes also from a study showing reactivity of peripheral blood mononuclear cells to a B27 peptide in patients with HLA-B27-associated uveitis (a disease related to spondylarthropathy) but not in controls (68). Furthermore, in an animal model of experimental uveitis, oral tolerance could be induced by feeding the animals the same B27 peptide (68).…”