Characterization of the murine H2-M3wt-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-M3wt. 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-M3wt within APC remains uncertain. HAA/lemA-immune effectors are unusually cross-reactive. We could readily detect H2-M3wt-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.
Kurlander
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R
Department of Medicine, Duke Medical Center, Durham, North Carolina 27710, USA. kurla001@mc.duke.edu
Nataraj
C
C
D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006183:H-2 Antigens / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology*; D009239:N-Formylmethionine / Q000276:immunology; D010743:Phospholipids / Q000276:immunology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D006183:H-2 Antigens; C101169:LemA protein, Listeria; D010743:Phospholipids; D009239:N-Formylmethionine