Definition of the HLA-A29 peptide ligand motif allows prediction of potential T-cell epitopes from the retinal soluble antigen, a candidate autoantigen in birdshot retinopathy.

Abstract

The peptide-binding motif of HLA-A29, the predisposing allele for birdshot retinopathy, was determined after acid-elution of endogenous peptides from purified HLA-A29 molecules.

Motif Inference Reveals Optimal CTL Epitopes Presented by HLA Class I Alleles Highly Prevalent in Southern Africa

“…Like the closely related A*3002, Tyr/Phe are the preferred residues at P2 and Tyr is preferred at PC. There is no HLA-A allele with a motif that incorporates a negatively charged residue at P2, and thus A*2902 would be unique if, as previously indicated (11), it were so. However, the failure to demonstrate binding to A*2902 of peptides conforming to this motif (with Glu at P2), in combination with the statistical implausibility of 16 of 16 eluted peptides having Glu at P2 compared with 0 of 5 defined A*2902-restricted epitopes ( p ϭ 4.9 ϫ 10 Ϫ5 ), would indicate that the true motif for A*2902 is Tyr/Phe at P2 and Tyr at PC.…”

Combination of KIR and HLA gene variants augments the risk of developing birdshot chorioretinopathy in HLA-A*29-positive individuals

“…Supporting this model was the elution of retinal autoantigens from HLA-A29 molecules. 55 Predominance of KIR2DS2, 2DS3 and 2DS4, the genes implicated in autoimmune diseases [56][57][58] in BCR patients compared to HLA-A*29-matched controls, suggests that these aKIR receptors may enhance the T-cell autoreactivity. Although the direct role of NK cells in BCR pathogenesis is not clear, the genetic data presented herein indicate that KIR-HLA combinations likely influence both CTL and NK cell responses toward tolerance in controls and autoimmunity in BCR patients ( Figure 5).…”

Differences in endogenous peptides presented by HLA-B*2705 and B*2703 allelic variants. Implications for susceptibility to spondylarthropathies.

“…The supernatant was precleared for 1 h with a mixture of 150 l 10% Pansorbin (Calbiochem Corp., San Diego, CA) and 2 l normal mouse serum. After centrifugation the supernatant was divided into aliquots and precipitated overnight with 10 g/ml of TAP2 specific 435.3 mAb kindly provided by Dr. P. van Endert (24), anti-B27 ME1 mAb (19) or anti HLA class1 W6/32 mAb (21). Immunoprecipitates were recovered with 20 l 50% protein A-sepharose beads and resolved on a 10% SDS-PAGE.…”

“…The procedure of HLA purification has been described (21). HLA-B27 molecules were captured on cyanogen bromide-activated Sepharose 4B columns (Pharmacia, Saint-Quentin en Yvelines, France) coupled to ME1 mAb.…”