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.
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.
Peptides encompassing amino acids Q1-C21 and D26-K50 of ICAM-1, I237-I261 and G441-G466 of the LFA-1 α-subunit, and D134-Q159 of the LFA-1 β-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.
Our data suggest that these peptides or their derivatives may be useful as therapeutic modulators of LFA-1/ICAM-1 interaction during organ transplants.
Department of Microbiology; Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas 66045
1 Supported in part by a grant from the American Heart Association, Kansas Chapter.
2 Department of Microbiology, University of Kansas, Lawrence, KS 66045.
3 Present address: Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
4 Department of Pharmaceutical Chemistry, University of Kansas.
5 Address correspondence to: Dr. Stephen H. Benedict, Department of Microbiology, University of Kansas, Lawrence, KS 66045. E-mail: firstname.lastname@example.org.
Received 14 September 1998.
Accepted 21 February 1999.