Development of Altered Peptide Ligands for Immunotherapy of Experimental Collagen-induced Arthritis (B96)

Abstract

Abstract Collagen-induced arthritis is an autoimmune disease that results from the immunization of susceptible mouse strains with type II collagen. Amino acid residues 260–274 in the bovine collagen II alpha chain (bCIIá) represent the major MHC Class II epitope for the human DR1 haplotype. Amino acid residues 267Q and 270K are predicted TCR contact residues. Replacement of either of these amino acids with a glycine does not alter the ability of the peptides to bind to soluble DR1 but does substantially decrease their ability to induce proliferation of lymphocytes from bCIIá-immunized B10.M.DR1 mice while still allowing them to interfere with bCIIá-induced proliferation. The altered peptides elicit moderate decreases in disease incidence when co-immunized with bCIIá or injected intraperitoneally prior to the onset of clinical signs of disease.