UNIQUE EPITOPE OF APOLIPOPROTEIN-A-I EXPRESSED IN PRE-BETA-1 HIGH-DENSITY-LIPOPROTEIN AND ITS ROLE IN THE CATALYZED EFFLUX OF CELLULAR CHOLESTEROL

The ability of mouse anti-apolipoprotein A-I (gpo A-I) monoclonal antibodies to recognize pre-beta-HDL species in native plasma was determined. An antibody identifying residues 137-144 of the mature protein uniquely recognized pre-beta-1 HDL, an HDL species of low molecular weight implicated in early cholesterol transport from cell membranes to plasma [Castro, G R., and Fielding, C. J. (1988) Biochemistry 27, 25-29]. Incubation of plasma with this antibody significantly inhibited the efflux-of labeled cholesterol from cultured fibroblast monolayers. A second antibody, binding to residues 93-99 of apo A-I, recognized a second pre-beta-HDL species (pre-beta-2 HDL) but not pre-beta-1 HDL and did not inhibit cholesterol efflux. Several other antibodies had broad Specificity for HDL (including pre-beta-1 HDL), This research suggests that apo A-I residues 137-144 are adjacent to or part of a structural site in pre-beta-1 HDL active in promoting the efflux of cellular cholesterol and that this site is not exposed in other HDL species.