Linear and cyclic LFA-1 and ICAM-1 peptides inhibit T cell adhesion and function.
Short peptides derived from functional proteins have been used in several instances to inhibit activity of the parent proteins. In some cases, stability and efficacy were found to be increased by cyclization of these peptides. Inhibition of interaction of the two cell adhesion counter receptors leukocyte function-associated antigen (LFA)-1 and intercellular adhesion molecule (ICAM)-1 is being studied as a method for modulating autoimmune diseases such as rheumatoid arthritis and for facilitating organ transplantation. Here, several 10-amino acid peptides derived from the contact domains of LFA-1 and ICAM-1 were evaluated for their ability to interfere with intercellular adhesion by T cells and to inhibit a more biologic, mixed lymphocyte reaction. Both linear and cyclic forms of the peptides were effective at inhibiting intercellular adhesion. Cyclic forms were effective at inhibiting T cell activation and proliferation in the mixed lymphocyte reaction.
Tibbetts
S A
SA
Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USA.
Seetharama Jois
D
D
Siahaan
T J
TJ
Benedict
S H
SH
Chan
M A
MA
D000595:Amino Acid Sequence; D018821:CD18 Antigens / Q000737:chemistry; D002448:Cell Adhesion; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000737:chemistry*; D008969:Molecular Sequence Data; D014066:Palatine Tonsil / Q000166:cytology; D010455:Peptides / Q000494:pharmacology*; D011485:Protein Binding; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects
D018821:CD18 Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D010455:Peptides; D018799:Intercellular Adhesion Molecule-1