DEFINITION OF THE HLA-A29 PEPTIDE LIGAND MOTIF ALLOWS PREDICTION OF POTENTIAL T-CELL EPITOPES FROM THE RETINAL SOLUBLE-ANTIGEN, A CANDIDATEAUTOANTIGEN IN BIRDSHOT RETINOPATHY

The peptide-binding motif of HLA-A29, the predisposing allele for bird shot retinopathy, was determined after acid-elution of endogenous pept ides from purified HLA A29 molecules, Individual and pooled HPLC fract ions were sequenced by Edman degradation. Major anchor residues could be defined as glutamate at the second position of the peptide and as t yrosine at the carboxyl terminus, In vitro binding of polyglycine synt hetic peptides to purified HLA-A29 molecules also revealed the need fo r an auxiliary anchor residue at the third position, preferably phenyl alanine, By using this motif, we synthesized six peptides from the ret inal soluble antigen, a candidate autoantigen in autoimmune uveoretini tis. Their in vitro binding was tested on HLA-A29 and also on HLA-B44 and HLA-B61, two alleles sharing close peptide-binding motifs, Two pep tides derived from the carboxyl-terminal sequence of the human retinal soluble antigen bound efficiently to HLA-A29. This study could contri bute to the prediction of T-cell epitopes from retinal autoantigens im plicated in birdshot retinopathy.