A 16mer peptide of the human autoantigen calreticulin is a most prominent HLA-DR4Dw4-associated self-peptide.
The human Ca(2+)-binding (storage) protein calreticulin, located in the lumen of the endoplasmic reticulum, is proposed to play a role as autoantigen: anticalreticulin autoantibodies occur in the sera of patients with SLE and patients with onchocerciasis (calreticulin shows a high sequence homology to the Onchocerca volvulus antigen RAL-1). Here we present sequencing data of a HLA-DR4Dw4-associated calreticulin peptide fragment, Cal(295-310), purified from a DR4Dw4 self-peptide pool. Cal(295-310) proved to be one of three commonest self-peptides associated with DR4Dw4 molecules that were isolated from the EBV-transformed B-cell line BSM (DR4Dw4, DRw53). We tested the binding of Cal(295-309) and the analogous RAL-1 peptide to HLA-DR molecules: Cal(295-309) exhibited specific binding characteristics for DR4Dw4. Binding assays using self-peptide analogues with replaced amino acids led us to a DR4Dw4-binding motif with anchor residues at relative positions 1 and 6. The sequencing data suggest that calreticulin is a frequently processed intracellular protein. The abundance of calreticulin makes the presentation of different calreticulin peptides associated with HLA-D molecules likely to occur, supporting the immunologic relevance of this molecule.
Medicine and Natural Sciences Research Center, University of Tübingen, Germany.
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H
Max
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Halder
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M
Kalbus
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Gnau
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G
Jung
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H
Kalbacher
D000595:Amino Acid Sequence; D001324:Autoantigens / Q000737:chemistry*; D001402:B-Lymphocytes; D001665:Binding Sites; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000276:immunology*; D037282:Calreticulin; D002461:Cell Line, Transformed; D002851:Chromatography, High Pressure Liquid; D015804:HLA-DR4 Antigen / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D012261:Ribonucleoproteins / Q000737:chemistry* / Q000276:immunology*
D001324:Autoantigens; D002135:Calcium-Binding Proteins; D037282:Calreticulin; D015804:HLA-DR4 Antigen; D012261:Ribonucleoproteins