THE MEMBRANE-PROXIMAL SCAVENGER RECEPTOR CYSTEINE-RICH DOMAIN OF CD6 CONTAINS THE ACTIVATED LEUKOCYTE CELL-ADHESION MOLECULE-BINDING SITE

Binding studies with a CD6 immunoglobulin fusion protein (CD6 Rg) resu lted in the identification and cloning of a CD6 ligand, This ligand wa s found to be a member of the immunoglobulin supergene family and was named ALCAM (activated leukocyte cell adhesion molecule), Cell adhesio n assays showed that CD6-ALCAM interactions mediate thymocyte-thymic e pithelium cell binding, ALCAM is also expressed by activated leukocyte s and neurons and may be involved in interactions between T cells and activated leukocytes and between cells of the immune and nervous syste ms, respectively. Herein we describe the preparation of domain-specifi c murine CD6 Rg fusion proteins and show that the membrane-proximal SR CR (scavenger receptor cysteine-rich) domain of CD6 contains the ALCAM binding site, We also show that mAbs which bind to this domain prefer entially block CD6-ALCAM binding. These results demonstrate that the m embrane-proximal SRCR do main of CD6 is necessary for CD6 binding to A LCAM and provide the first direct evidence for the interaction of an S RCR domain with a ligand.