The ability of mouse anti-apolipoprotein A-I (apo A-I) monoclonal antibodies to recognize pre-β-HDL species in native plasma was determined. An antibody identifying residues 137-144 of the mature protein uniquely recognized pre-β-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-β-HDL species (pre-β-2 HDL) but not pre-β-1 HDL and did not inhibit cholesterol efflux. Several other antibodies had broad specificity for HDL (including pre-β-1 HDL). This research suggests that apo A-I residues 137-144 are adjacent to or part of a structural site in pre-β-1 HDL active in promoting the efflux of cellular cholesterol and that this site is not exposed in other HDL species.
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