EXPRESSION OF THE H52 EPITOPE ON THE BETA-2 SUBUNIT IS DEPENDENT ON ITS INTERACTION WITH THE ALPHA-SUBUNITS OF THE LEUKOCYTE INTEGRINS LFA-1, MAC-1 AND P150,95 AND THE PRESENCE OF CA2+

Integrin-mediated adhesion is a divalent cation-dependent process. Whe ther divalent cations directly participate in ligand binding or exert their effects indirectly by affecting the overall structure of the int egrin heterodimers is not known. In this study we describe the epitope of the mAb H52 which has been mapped to a predicted disulfide-bonded loop (C386 and C400) in the beta 2 integrin subunit. In the presence o f Ca2+ and Mg2+, the H52 epitope is expressed on the monomeric beta 2 subunit, the LFA-1 and Mac-1 heterodimers but not on p150,95, thus imp lying that this epitope is masked in p150,95. However, expression of t he H52 epitope on Mac-1, but not on LFA-1, or the monomeric beta 2 sub unit, is dependent on the presence of Ca2+, thus suggesting that the c helation of Ca2+ causes a conformation at change in Mac-1 which result s in the loss of the epitope. These results suggest that expression of the H52 epitope on the beta 2 subunit is dependent on its interaction with the different alpha subunits. Since the epitope itself is not re quired for heterodimer formation nor for ligand binding, occupancy of a Ca2+ binding site(s) must therefore affect the alpha beta subunit in teractions, and thus the overall conformation of Mac-1.