THE AMINO-TERMINAL IMMUNOGLOBULIN-LIKE DOMAIN OF ACTIVATED LEUKOCYTE CELL-ADHESION MOLECULE BINDS SPECIFICALLY TO THE MEMBRANE-PROXIMAL SCAVENGER RECEPTOR CYSTEINE-RICH DOMAIN OF CD6 WITH A 1 1 STOICHIOMETRY/

Activated leukocyte cell adhesion molecule (ALCAM) was recently identi fied as a ligand for CD6, a signaling receptor expressed on T cells, a subset of B cells, and some cells in the brain. Receptor-Ligand bindi ng assays, antibody blocking experiments, and examination of the tissu e distribution of these two cell surface proteins suggest that CD6-ALC AM interactions play an important role in mediating the binding of thy mocytes to thymic epithelial cells and of T cells to activated leukocy tes. Presently, the details of CD6-ALCAM interactions and of signaling through CD6 are unknown, A series of truncated human ALCAM and CD6 im munoglobulin fusion proteins were produced and tested in different bin ding assays to analyze ALCAM-CD6 interactions in more detail, In this study, we report that the amino-terminal Ig-like domain of human ALCAM specifically binds to the third membrane-proximal scavenger receptor cysteine-rich (SRCR) domain of human CD6. Using thrombin-cleaved Ig fu sion proteins containing single or multiple ALCAM or CD6 domains, we w ere able to determine that the stoichiometry of the interaction betwee n the amino-terminal ALCAM domains and the membrane-proximal CD6 SRCR domain is 1:1. These results provide the first example of an Ig-like d omain mediating an interaction with an SRCR domain.