The pathogenesis of atherosclerosis involves innate and adaptive immune responses. A high blood level of low-density lipoproteins (LDLs) is considered a major risk factor for atherosclerosis due to increased subendothelial retention of LDL particles, their modification, and the production of new autoantigens that trigger maladaptive immune responses in the arterial wall [1,2]. In this context, a subfraction of modified LDLs found in blood and characterized by high electronegativity [3,4,5] is called electronegative LDL [LDL (−)], and has been shown to trigger proinflammatory responses in endothelial cells and macrophages [6,7,8,9]. More recently, LDL (−) has been found to interact with CD14 and TLR4 in human monocytes and macrophages, which implicates LDL (−) as a potential important transducer of proinflammatory effects [10]. In addition to affecting innate immune responses, LDL (−) and its autoantibodies have been detected in blood plasma and atherosclerotic lesions of humans and rabbits [11,12]. Although different lipids derived from LDL have been identified as triggers of inflammatory responses, some studies have indicated that the LDL protein moiety can be bioactive. Several peptides derived from apoB-100 have been shown to activate T and B cells [13,14,15] and also demonstrated anti-inflammatory activity [16]. Another peptide, apoB-100 danger associated signal 1 (ApoBDS-1) has been shown to induce the release of IL-6, IL-8, and CCL2 by monocytes, macrophages, and atherosclerotic plaque cultures [14] as well as activate platelets [17]. In previous work, we described two monoclonal antibodies (mAbs), 1A3 and 2C7, capable of recognizing different epitopes of LDL (−). These mAbs were used to develop ELISA-based assays for the quantification of LDL (−) and its autoantibodies [18]. Using these assays, we showed that LDL (−) and its autoantibodies were increased in individuals with high atherosclerosis risk, such as chronic coronary syndromes [19]. Furthermore, passive immunization with these anti-LDL (−) antibodies has been shown to be atheroprotective in Ldlr −/− mice [20]. Following this work, other studies have produced an anti-LDL (−) single-chain fragment variable (scFv) of the 2C7 monoclonal antibody that has potential applications in atherosclerosis therapy and diagnosis [21,22,23]. However, the molecular properties of immunodominant proinflammatory epitopes of LDL (−) remain unknown. In this study we mapped epitopes of LDL (−) recognized by the 1A3 and 2C7 mAbs in a phage display library and investigated their capacity to stimulate macrophages in vitro.