The macrophage-TCR alpha beta is a cholesterol-responsive combinatorial immune receptor and implicated in atherosclerosis

Recent evidence indicates constitutive expression of a recombinatorial TCR alpha beta immune receptor in mammalian monocytes and macrophages. Here, we demonstrate in vitro that macrophage-TCR beta repertoires are modulated by atherogenic low density cholesterol (LDL) and high-density cholesterol (HDL). In vivo, analysis of freshly obtained artery specimens from patients with severe carotid atherosclerosis reveals massive abundance of TCR alpha beta + macrophages within the atherosclerotic lesions. Experimental atherosclerosis in mouse carotids induces accumulation of TCR bearing macrophages in the vascular wall and TCR deficient rag-/- mice have an altered macrophage-dependent inflammatory response. We find that the majority of TCR alpha beta bearing macrophages are localized in the hot spot regions of the atherosclerotic lesions. Advanced carotid artery lesions express highly restricted TCR alpha beta repertoires that are characterized by a striking usage of the V beta 22 and V beta 16 chains. This together with a significant degree of interindividual lesion repertoire sharing suggests the existence of atherosclerosis-associated TCR alpha beta signatures. Our results implicate the macrophage-TCR alpha beta combinatorial immunoreceptor in atherosclerosis and thus identify an as yet unknown adaptive component in the innate response-to-injury process that underlies this macrophage-driven disease.