Autoimmune disorders, that occur when autoreactive immune cells are induced to activate their responses against self-tissues, affect one percent of the world population and represent one of the top 10 leading causes of death. The major histocompatibility complex (MHC) is a principal susceptibility locus for many human autoimmune diseases, in which self-tissue antigens providing targets for pathogenic lymphocytes are bound to HLA molecules encoded by disease-associated alleles. In spite of the attempts to design strategies for inhibition of antigen presentation targeting the MHC-peptide/TCR complex via generation of blocking antibodies, altered peptide ligands (APL), or inhibitors of costimulatory molecules, potent therapies with minimal side effects have yet to be developed. Copaxone (glatiramer acetate, GA) is a random synthetic amino acid copolymer that reduces the relapse rate by about 30% in relapsing-remitting multiple sclerosis (MS) patients. Based on the elucidated binding motifs of Copaxone and of the anchor residues of the immunogenic myelin basic protein (MBP) peptide to HLA-DR molecules, novel copolymers have been designed and proved to be more effective in suppressing MS-like disease in mice. In this report, we describe the rationale for design of second-generation synthetic random copolymers as candidate drugs for a number of MHC class-II-associated autoimmune disorders.
机构:From the Division of Rheumatology, Department of Medicine, University of Heidelberg, and from the Departments of Immunology and Medicine/Rheumatology, Mayo Clinic and Foundation, Rochester, MN
WEYAND, CM
JENDRO, M
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机构:From the Division of Rheumatology, Department of Medicine, University of Heidelberg, and from the Departments of Immunology and Medicine/Rheumatology, Mayo Clinic and Foundation, Rochester, MN
JENDRO, M
GORONZY, JJ
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机构:From the Division of Rheumatology, Department of Medicine, University of Heidelberg, and from the Departments of Immunology and Medicine/Rheumatology, Mayo Clinic and Foundation, Rochester, MN
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Univ Texas San Antonio, Dept Biol, One UTSA Circle, San Antonio, TX 78249 USAUniv Texas San Antonio, Dept Biol, One UTSA Circle, San Antonio, TX 78249 USA
Nalawade, Saisha A.
Ji, Niannian
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Univ Texas Hlth, Sch Med, Dept Urol, San Antonio, TX 78229 USAUniv Texas San Antonio, Dept Biol, One UTSA Circle, San Antonio, TX 78249 USA
Ji, Niannian
Raphael, Itay
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Univ Pittsburgh, Dept Med, 930 Scaife Hall, Pittsburgh, PA 15261 USAUniv Texas San Antonio, Dept Biol, One UTSA Circle, San Antonio, TX 78249 USA
Raphael, Itay
Pratt, Andrew, III
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US Naval Med Res Unit, San Antonio, TX 78234 USAUniv Texas San Antonio, Dept Biol, One UTSA Circle, San Antonio, TX 78249 USA
Pratt, Andrew, III
Kraig, Ellen
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Univ Texas Hlth, Dept Cell Syst & Anat, San Antonio, TX 78229 USAUniv Texas San Antonio, Dept Biol, One UTSA Circle, San Antonio, TX 78249 USA
Kraig, Ellen
Forsthuber, Thomas G.
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Univ Texas San Antonio, Dept Biol, One UTSA Circle, San Antonio, TX 78249 USAUniv Texas San Antonio, Dept Biol, One UTSA Circle, San Antonio, TX 78249 USA
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Univ Colorado Denver, Human Med Genet Program, Sch Med, Aurora, CO 80045 USA
Univ Colorado Denver, Dept Pediat, Sch Med, Aurora, CO 80045 USAUniv Colorado Denver, Human Med Genet Program, Sch Med, Aurora, CO 80045 USA
Jin, Ying
Birlea, Stanca A.
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Univ Colorado Denver, Human Med Genet Program, Sch Med, Aurora, CO 80045 USA
Univ Colorado Denver, Dept Dermatol, Sch Med, Aurora, CO 80045 USAUniv Colorado Denver, Human Med Genet Program, Sch Med, Aurora, CO 80045 USA
Birlea, Stanca A.
Fain, Pamela R.
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Univ Colorado Denver, Human Med Genet Program, Sch Med, Aurora, CO 80045 USA
Univ Colorado Denver, Dept Pediat, Sch Med, Aurora, CO 80045 USA
Univ Colorado Denver, Barbara Davis Ctr Childhood Diabet, Sch Med, Aurora, CO 80045 USAUniv Colorado Denver, Human Med Genet Program, Sch Med, Aurora, CO 80045 USA
Fain, Pamela R.
Gowan, Katherine
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Univ Colorado Denver, Human Med Genet Program, Sch Med, Aurora, CO 80045 USAUniv Colorado Denver, Human Med Genet Program, Sch Med, Aurora, CO 80045 USA
Gowan, Katherine
Riccardi, Sheri L.
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Univ Colorado Denver, Human Med Genet Program, Sch Med, Aurora, CO 80045 USAUniv Colorado Denver, Human Med Genet Program, Sch Med, Aurora, CO 80045 USA
Riccardi, Sheri L.
Holland, Paulene J.
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Univ Colorado Denver, Human Med Genet Program, Sch Med, Aurora, CO 80045 USAUniv Colorado Denver, Human Med Genet Program, Sch Med, Aurora, CO 80045 USA
Holland, Paulene J.
Bennett, Dorothy C.
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Univ London, Div Basic Med Sci, London, EnglandUniv Colorado Denver, Human Med Genet Program, Sch Med, Aurora, CO 80045 USA
Bennett, Dorothy C.
Herbstman, Deborah M.
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Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL USAUniv Colorado Denver, Human Med Genet Program, Sch Med, Aurora, CO 80045 USA
Herbstman, Deborah M.
Wallace, Margaret R.
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Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL USAUniv Colorado Denver, Human Med Genet Program, Sch Med, Aurora, CO 80045 USA
Wallace, Margaret R.
McCormack, Wayne T.
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Univ Florida, Coll Med, Dept Pathol Immunol & Lab Med, Gainesville, FL USAUniv Colorado Denver, Human Med Genet Program, Sch Med, Aurora, CO 80045 USA
McCormack, Wayne T.
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Kemp, E. Helen
Gawkrodger, David J.
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Royal Hallamshire Hosp, Dept Dermatol, Sheffield S10 2JF, S Yorkshire, EnglandUniv Colorado Denver, Human Med Genet Program, Sch Med, Aurora, CO 80045 USA
Gawkrodger, David J.
Weetman, Anthony P.
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Univ Sheffield, Sch Med, Dept Human Metab, Sheffield, S Yorkshire, EnglandUniv Colorado Denver, Human Med Genet Program, Sch Med, Aurora, CO 80045 USA
Weetman, Anthony P.
Picardo, Mauro
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Ist Dermatol S Maria & S Gallicano, Lab Fisiopatol Cutanea, Rome, ItalyUniv Colorado Denver, Human Med Genet Program, Sch Med, Aurora, CO 80045 USA
Picardo, Mauro
Leone, Giovanni
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Ist Dermatol S Maria & S Gallicano, Lab Fisiopatol Cutanea, Rome, ItalyUniv Colorado Denver, Human Med Genet Program, Sch Med, Aurora, CO 80045 USA
Leone, Giovanni
Taieb, Alain
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Hop St Andre, Dept Dermatol, Ctr Reference Malad Rares Peau, Bordeaux, FranceUniv Colorado Denver, Human Med Genet Program, Sch Med, Aurora, CO 80045 USA
Taieb, Alain
Jouary, Thomas
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Hop St Andre, Dept Dermatol, Ctr Reference Malad Rares Peau, Bordeaux, FranceUniv Colorado Denver, Human Med Genet Program, Sch Med, Aurora, CO 80045 USA
Jouary, Thomas
Ezzedine, Khaled
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Hop St Andre, Dept Dermatol, Ctr Reference Malad Rares Peau, Bordeaux, FranceUniv Colorado Denver, Human Med Genet Program, Sch Med, Aurora, CO 80045 USA
Ezzedine, Khaled
van Geel, Nanny
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Ghent Univ Hosp, Dept Dermatol, Ghent, BelgiumUniv Colorado Denver, Human Med Genet Program, Sch Med, Aurora, CO 80045 USA
van Geel, Nanny
Lambert, Jo
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Ghent Univ Hosp, Dept Dermatol, Ghent, BelgiumUniv Colorado Denver, Human Med Genet Program, Sch Med, Aurora, CO 80045 USA
Lambert, Jo
Overbeck, Andreas
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Lumiderm, Madrid, SpainUniv Colorado Denver, Human Med Genet Program, Sch Med, Aurora, CO 80045 USA
Overbeck, Andreas
Spritz, Richard A.
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Univ Colorado Denver, Human Med Genet Program, Sch Med, Aurora, CO 80045 USA
Univ Colorado Denver, Dept Pediat, Sch Med, Aurora, CO 80045 USAUniv Colorado Denver, Human Med Genet Program, Sch Med, Aurora, CO 80045 USA