Generation of self-peptides to treat systemic lupus erythematosus.
Synthetic peptides are attracting increasing attention as therapeutics. Despite their potential, however, only a few selected peptides have been able to enter in clinical trials for chronic autoimmune diseases and systemic lupus erythematosus (SLE) in particular. Here, we describe and discuss a series of assays, which may help in characterizing valuable candidate peptides that were applied in our laboratory to develop the lupus P140 peptide program. The different steps of selection include the choice of the initial autoantigen, the design, synthesis and purification of peptides, their preliminary screen by measuring cytokines produced ex vivo by T cells and their binding to major histocompatibility complex class II (MHCII) molecules, their capacity to lower peripheral cell hyperproliferation in lupus-prone MRL/lpr mice, and, as a final step, their ability to slow down the development of lupus disease in model animals.
Immunopathology and Therapeutic Chemistry, CNRS, Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France.
Jean-Paul
JP
Briand
Nicolas
N
Schall
Sylviane
S
Muller
D000818:Animals; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D010455:Peptides / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D011485:Protein Binding / Q000276:immunology
D001324:Autoantigens; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D010455:Peptides