Characterization of the murine H2-M3(wt)-restricted CD8 response against a hydrophobic, protease-resistant, phospholipid-associated antigen from Listeria monocytogenes

Mice infected with Listeria monocytogenes (LM) generate protective CD8 cells of varying specificity. One subset, unlike conventional LM-immune CD8 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 class Ib product H2-M3(wt). HAA proved to be extremely hydrophobic and the bioactive portion of the molecule was highly protease-resistant, reading 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, bur the site where antigen binds to H2-M3(wt)within APC remains uncertain. HAA/lemA-immune effecters are unusually cross-reactive. We could readily detect H2-M3(wt)-restricted responses to APC incubated with unrelated N-formylated peptides, and bacteria. HP,A-like products represent an intriguing new set of bacterial antigens recognizable by immune CD8 cells.