Disease inhibition by major histocompatibility complex binding peptide analogues of disease-associated epitopes: more than blocking alone.
Peptide analogues of disease-associated epitopes were studied for inhibition of experimental allergic encephalomyelitis (EAE) and adjuvant arthritis (AA) in Lewis rats. EAE- and AA-associated analogues were selected as competitors because of their in vitro inhibitory activity on proliferation of encephalitogenic and arthritogenic T cells. Although the EAE-associated competitor had a superior major histocompatibility complex (MHC) binding affinity, the AA-associated competitor was a better inhibitor of the in vitro proliferation of arthritogenic T cells. Furthermore, although in vivo EAE was inhibited by both competitors, AA was only inhibited by the AA-associated competitor. Remarkably, in contrast to what was expected of a regular MHC competitor peptide, the AA-associated peptide analogue also prevented AA upon immunization before disease induction and appeared to induce T cell responses that crossreacted with the original disease-associated epitope. Therefore, it is concluded that antigen-specific regulatory mechanisms were involved in synergy with MHC competition. The integration of both qualities into a single "competitor-modulator" analogue peptide may lead to the development of novel, more effective, disease-specific immunomodulatory peptides.
Wauben
M H
MH
Institute of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, University of Utrecht, The Netherlands.
Boog
C J
CJ
van der Zee
R
R
Joosten
I
I
Schlief
A
A
van Eden
W
W
D000409:Alanine / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology*; D001667:Binding, Competitive; D002455:Cell Division; D002460:Cell Line; D002999:Clone Cells; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D007113:Immunity, Innate; D008285:Major Histocompatibility Complex / Q000276:immunology*; D008297:Male; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
D000939:Epitopes; D010455:Peptides; D000409:Alanine