PEPTIDES FROM THE AMINO-TERMINUS OF RANTES CAUSE CHEMOTAXIS OF HUMAN T-LYMPHOCYTES

RANTES is a potent chemotactic and activating agent for a variety of l eukocytes including T-lymphocytes. To identify the region of the molec ule responsible for this activity, we have made overlapping 10 amino a cid peptides scanning the protein. A micro-Boyden chamber chemotaxis a ssay showed the most efficacious peptides came from at the N-terminus. EC(50) values of 8 nM (+/- 2.2 nM), 3.7 nM (+/- 2.0 nM) and 3.1 nM (/- 2.0 nM) were calculated fi om dose response curves for the peptides (1-10), (3-12), and (5-14). Control peptides from other regions are n ot active. In THP-1 cells, none of the peptides give a Ca2+ response. The active peptides are shown to be principally chemotactic rather tha n chemokinetic by a checker board analysis. The results imply that the principal region of RANTES responsible for chemotaxis is located in t he amino terminus. (C) 1995 Academic Press, Inc.