A 16MER PEPTIDE OF THE HUMAN AUTOANTIGEN CALRETICULIN IS A MOST PROMINENT HLA-DR4DW4-ASSOCIATED SELF-PEPTIDE

The human Ca2+-binding (storage) protein calreticulin, located in the lumen of the endoplasmic reticulum, is proposed to play a role as auto antigen: 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 p resent sequencing data of a HLA-DR4Dw4-associated calreticulin peptide fragment, Cal(235-310), 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-c ell line BSM (DR4Dw4, DRw53). We rested the binding of Cal(295-309) an d the analogous RAL-1 peptide to HLA-DR molecules: Cal(295-309) exhibi ted specific binding characteristics for DR4Dw4. Binding assays using self-peptide analogues with replaced amino acids led us to a DR4Dw4-bi nding motif with anchor residues at relative positions 1 and 6. The se quencing data suggest that calreticulin is a frequently processed intr acellular protein. The abundance of calreticulin makes the presentatio n of different calreticulin peptides associated with HLA-D molecules l ikely to occur, supporting the immunologic relevance of this molecule.