CHARACTERIZATION OF THE MURINE H2-M3(WT)-RESTRICTED CD8 RESPONSE AGAINST A HYDROPHOBIC, PROTEASE-RESISTANT, PHOSPHOLIPID-ASSOCIATED ANTIGENFROM LISTERIA-MONOCYTOGENES

Mice infected with Listeria monocytogenes (LM) generate protective CD8 cells of varying specificity. One subset, unlike conventional LM-immu ne CD8 cells, can respond to antigen-presenting cells (APC) treated wi th heat-killed LM (HKLM). These cells proved to have surprisingly unif orm specificity recognizing a product we designated HKLM-associated an tigen (HAA) presented by the non-classical class Ib product H2-M3(wt). HAA proved to be extremely hydrophobic and the bioactive portion of t he molecule was highly protease-resistant, reading us initially to spe culate that it might be a non-peptide. Recent studies, however, identi fy HAA as a complex containing lemA, a listerial protein bearing the i mmunogenic amino terminal peptide sequence fMIGWII, tightly associated with bacterial cardiolipin. A variety of cell types can process and p resent exogenous HAA/lemA, and the phospholipid component appears esse ntial 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 response s to APC incubated with unrelated N-formylated peptides, and bacteria. HP,A-like products represent an intriguing new set of bacterial antig ens recognizable by immune CD8 cells.