Characterization of the murine H2–M3wt-restricted CD8 response against a hydrophobic, protease-resistant, phospholipid-associated antigen from Listeria monocytogenes

Summary: Mice infected with Listeria monocytogenes (LM) generate protective CD8 cells of varying specificity. One subset, unlike conventional LM-immune CDS cells, can respond to antigen-presenting cells (APC) treated with heat-killed LM (HKLM), These cells proved to have surprisingly uniform specificity, recognizing a product we designated HKLM-associated antigen (HAA) presented by the non-classical dass Ib product H2–M3'. HAA proved to be extremely hydrophobic and the bioactive portion of the molecule was highly protease-resistant, leading us initially to speculate that it might be a non-peptide. Recent studies, however, identify HAA as a complex containing lemA, a listerial protein bearing the immunogenic amino terminal peptide sequence fMIGWII, tightly associated with bacterial cardiolipin. A variety of cell types can process and present exogenous HAA/lemA. and the phospholipid component appears essential for this processing. Endosomal acidification and proteolysis are required for processing, but the site where antigen binds to H2–M3^wt within APC remains uncertain. HAA/lemA-immune effectors are unusually cross-reactive. We could readily detect H2–M3^wt-restricted responses to APC incubated with unrelated N -formylated peptides, and bacteria, HAA-like products represent an intriguing new set of bacterial antigens recognizable by immune CD8 cells.