An analog peptide that suppresses collagen-induced arthritis.
The authors undertook the identification of peptides capable of altering the immune response to type II collagen (CII) in the context of HLA-DR, as suppressing the immune response to CII could clarify the role of CII autoimmunity in the pathogenesis of disease. To produce synthetic peptides with the potential of disrupting the DR1-restricted immune response, synthetic analog peptides were developed that contain site-directed substitutions in critical positions. When these analog peptides were used to treat collagen-induced arthritis in DR1 transgenic mice, an analog peptide, CII 256-276 (N, D), was identified that inhibited T-cell responses in vitro. The data from studies with this analog peptide establish that CII 256-276 (N, D) is a potent suppressor of the DR-mediated immune response to CII and that its effect is mediated, at least in part, by interleukin-4. An analog peptide of CII recognized by T cells in the context of a human major histocompatibility complex molecule should have therapeutic significance for autoimmune arthritis.
Myers
Linda K
LK
Department of Pediatrics and Medicine, University of Tennessee, and from the Research Service of the Veterans Affairs Medical Center, Memphis, Tennessee, USA. lmyers@utmem.edu
Sakurai
Yoshihiko
Y
Rosloniec
Edward F
EF
Stuart
John M
JM
Kang
Andrew H
AH
D000595:Amino Acid Sequence; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy*; D024043:Collagen Type II / Q000276:immunology / Q000378:metabolism; D015798:HLA-DR1 Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D008285:Major Histocompatibility Complex; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D024043:Collagen Type II; D015798:HLA-DR1 Antigen; D010455:Peptides; D015847:Interleukin-4