Induction of arthritis and uveitis in Lewis rats by antigenic mimicry of peptides from HLA-B27 and cytokeratin

Wildner, Gerhild; Diedrichs-Möhring, Maria; Thurau, Stephan

doi:10.1002/1521-4141(200201)32:1<299::aid-immu299>3.0.co;2-q

Cited by 27 publications

(18 citation statements)

References 26 publications

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Krause

Altenburg

et al. 2008

Eye

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Purpose To evaluate the association of HLA-B51 and ocular involvement in Adamantiades-Behçet's disease. Methods We retrospectively analysed all patients with Adamantiades-Behçet's disease examined in our Department of Ophthalmology since 1982. All patients fulfilled the criteria of the International Study Group for Behçet's disease. We included 140 patients (63 female and 77 male) with a mean follow-up of 6.4 years. Results The mean age at the first manifestation was 23 years; full disease was noted at 32 years. The mean age at the time of eye involvement was 30 years. Most of the patients were of Turkish (n ¼ 73) or German (n ¼ 34) origin. A total of 56% patients developed eye involvement. Forty-nine out of 76 HLA-B51-positive patients (64.5%) and 26 out of 60 HLA-B51-negative patients (43.3%; P ¼ 0.014) developed ocular involvement. Conclusion More than the half of the patients with Adamantiades-Behçet's disease evaluated in our department developed ocular involvement. There was a statistically significantly higher frequency of HLA-B51 in these patients.

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Section: Discussionmentioning

confidence: 99%

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

Krause

Altenburg

et al. 2008

Eye

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“…In view of the marked increase in the expression of ␤ 2 m-free HLA-I HC expressing the mAb HC-10-defined epitope following T cell activation (5), it is tempting to speculate that following immune system activation, this epitope may trigger B and/or T cell-mediated autoimmune responses. If this interpretation is correct, the mAb HC-10-defined epitope may play a role in the induction of the auto-anti-␤ 2 m-free HLA-I HC Abs found in the course of HIV infection (26) and provides a mechanism for the arthritogenic properties of the cytokeratin cross-reactive HLA-B27-derived peptide (spanning amino acids 60 -72) (27), which partially overlaps the mAb HC-10-specific epitope. The close relationship between the arthritogenic and the mAb HC-10-specific epitopes of HLA-I HC may account for the ability of mAb HC-10 to prevent spontaneous inflammatory disease in HLA-B27 transgenic (B27 ϩ ␤ 2 m°) mice (13).…”

Section: Discussionmentioning

confidence: 99%

β2-Microglobulin-Free HLA Class I Heavy Chain Epitope Mimicry by Monoclonal Antibody HC-10-Specific Peptide

Perosa

Luccarelli

Prete

et al. 2003

The Journal of Immunology

150

163

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mAb HC-10 loses its reactivity with HLA class I (HLA-I) H chain (HC) following its association with β2-microglobulin (β2m). Furthermore, the HC-10 defined epitope appears to be involved in the pathogenesis of spondyloarthropathies, because HC-10 reduced their incidence in HLA-B27+β2m°/MHC class II knockout mice. This study has characterized the determinant recognized by HC-10. Panning of a phage display peptide library with HC-10 resulted in isolation of the motif PxxWDR, which could be aligned with P57, W60, D61, and R62 of the first domain of the HLA-I HC allospecificities reactive with HC-10. The 55EGPEYWDR(N/E)T64 (p-1) is the shortest motif-bearing peptide that reacts with HC-10 and inhibits its binding to soluble HLA-B7 HC, irrespective of whether N (p-1a) or E (p-1b) is present at position 63. By contrast, HC-10 did not react with six additional peptides, each bearing motif amino acid substitutions present in HC-10-not-reactive HLA-I allospecificities. The p-1-derived Qp-1, synthesized with the additional conserved Q54, which displays the highest in vitro reactivity with HC-10, was the only one to induce in mice IgG resembling HC-10 in their fine specificity. Mapping of the HC-10-defined determinant suggests that the lack of mAb reactivity with β2m-associated HLA-I HC is caused by blocking by the peptide in the groove of β2m-associated HLA-I HC, though a role of HC conformational changes following its association with β2m cannot be excluded. This information contributes to our understanding of the molecular basis of the antigenic profiles of β2m-free and β2m-associated HLA-I HC and may serve to develop active specific immunotherapy of spondyloarthropathies.

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“…Cross-reactivity of T cells between peptide antigens is the basis for molecular mimicry, a mechanism that is proposed to initiate autoimmunity. We have previously described HLA class I-derived peptides that mimic retinal (B27PD/PDSAg from retinal S-antigen) or synovial (B2702PA/Ker333 from cytokeratin) antigens, cause uveitis (10,14) or arthritis (11), and may also be used therapeutically as oral tolerogens in uveitis patients (8) and rats (11,14). Additional uveitogenic peptides that resemble retinal autoantigen peptide PDSAg can be derived from environmental antigens, such as rotavirus-or food-derived peptides (from bovine milk casein).…”

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confidence: 99%

“…1 in complete Freund's adjuvant as described previously (11) (only PDSAg was used at a dose of 20 g per rat). Ten days later, the animals underwent daily clinical examination, and arthritis and uveitis were graded as described previously (2,11). Histological uveitis grading was performed with cryosections of eyes stained for CD4 (14).…”

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confidence: 99%