Inhibition of T cell activation by MHC blockade: a possible strategy for immunointervention in autoimmune diseases.
Autoimmune diseases result from the activation of self-reactive T cells induced by autoantigens or by foreign antigens cross-reactive with an autoantigen. A striking characteristic of autoimmune diseases is the increased frequency of certain HLA alleles in affected individuals. Moreover, as demonstrated for example in rheumatoid arthritis and insulin-dependent diabetes mellitus, class II alleles positively associated with autoimmune diseases share amino acid residues in the hypervariable HLA regions involved in peptide binding. Therefore, it is likely that disease-associated HLA class II molecules have the capacity to bind the autoantigen and present it to T cells, thereby inducing and maintaining, under appropriate conditions, the autoimmune disease. The data reviewed here demonstrate MHC-selective inhibition of antigen-induced T cell responses in vivo by parenterally administered soluble, MHC-binding peptide competitors, under conditions in which the competitor is not immunogenic. This suggests the feasibility of a therapeutic approach based on blockade of MHC class II molecules in the treatment of HLA-linked autoimmune diseases.
Adorini
L
L
Preclinical Research, Sandoz Pharma Ltd., Basel, Switzerland.
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000517:prevention & control*; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D008285:Major Histocompatibility Complex / Q000187:drug effects* / Q000276:immunology*; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology*
D006680:HLA Antigens