Altered influenza virus haemagglutinin peptides inhibit T cell responses to type II collagen in rheumatoid arthritis

Rheumatoid arthritis (RA) is a T cell mediated autoimmune disease and associated with HLA-DR4 or HLA-DR1 subtypes.1,2 Type II collagen (CII) has been implicated as an autoantigen of RA, and CD4+ T cell responses to CII or CII derived peptides are mainly presented by HLA-DR4/1 molecules.3,4 Inhibition of antigen presentation by HLA-DR4/1 molecules can interfere with T cell mediated autoimmune responses in RA. Our previous studies have suggested that altered CII263–272 peptides inhibited CII263–272-induced T cell activation by blocking antigen presentation.5,6 In this study we examine the role of the altered influenza virus haemagglutinin (HA) 308–317 peptides (altered peptide ligands (APLs)) with single or multiple substitutions of T cell receptor (TCR) contact residues in T cell responses of peripheral blood mononuclear cells (PBMC) and inhibitory effects of APLs on CII263–272-induced T cell activation in RA. Twenty seven HLA-DR4/1 positive patients with RA (21 female, 6 male; mean (SD) age …