Peptides derived from ICAM-1 and LFA-1 modulate T cell adhesion and immune function in a mixed lymphocyte culture.
BACKGROUND
The counter receptors intercellular adhesion molecule (ICAM)-1 and lymphocyte function-associated antigen (LFA)-1 are lymphocyte cell surface adhesion proteins the interaction of which can provide signals for T cell activation. This binding event is important in T cell function, migration, and general immune system regulation. The ability to inhibit this interaction with monoclonal antibodies has proved to be therapeutically useful for several allograft rejection and autoimmune disease models.


METHODS
Short peptides representing counter-receptor contact domains of LFA-1 and ICAM-1 were examined for their ability to inhibit T cell adhesion and T cell function.


RESULTS
Peptides encompassing amino acids Q1-C21 and D26-K50 of ICAM-1, I237-I261 and G441-G466 of the LFA-1 alpha-subunit, and D134-Q159 of the LFA-1 beta-subunit inhibited LFA-1/ICAM-1-dependent adhesion in a phorbol-12,13-dibutyrate-induced model of tonsil T cell homotypic adhesion. This inhibition was specific to the peptide sequence and occurred without stimulation of T cell proliferation. The peptides also were effective in preventing T cell function using a one-way mixed lymphocyte reaction model for bone marrow transplantation.


CONCLUSIONS
Our data suggest that these peptides or their derivatives may be useful as therapeutic modulators of LFA-1/ICAM-1 interaction during organ transplants.
Tibbetts
S A
SA
Department of Microbiology, University of Kansas, Lawrence 66045, USA.
Chirathaworn
C
C
Nakashima
M
M
Jois
D S
DS
Siahaan
T J
TJ
Chan
M A
MA
Benedict
S H
SH
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D019556:COS Cells / Q000378:metabolism / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000494:pharmacology*; D018655:Lymphocyte Count / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D016169:Lymphocyte Function-Associated Antigen-1 / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology*; D014162:Transfection
D016169:Lymphocyte Function-Associated Antigen-1; D010446:Peptide Fragments; D018799:Intercellular Adhesion Molecule-1