title: H2M3wt-restricted, Listeria monocytogenes-immune CD8 T cells respond to multiple formylated peptides and to a variety of gram-positive and gram-negative bacteria.
abstract: A subset of H2M3wt-restricted, Listeria monocytogenes (LM)-immune CD8 effectors recognize antigen-presenting cells (APC) preincubated with heat-killed LM. The responsible product, which we have previously designated heat-killed Listeria-associated antigen (HAA), is extremely hydrophobic and resistant to proteolytic degradation. Despite the protease resistance of HAA, we now report that HAA-immune clones are uniformly responsive to fMIGWII, a formylated oligopeptide derived from the recently described LM product, lemA. While fMIGWII was by far the most potent peptide tested, over half our clones also responded to the LM-derived peptide fMIVII and cross-reactive responses to two other unrelated formylated peptides at concentrations of <1 microM were frequently observed. One of these peptides (fBlaZ) did not share any amino acid in common with fMIGWII except N-formyl methionine at position 1. Unformylated variants of the same peptides were inactive. HAA-immune CD8 cells also responded in an H2M3wt-restricted manner to APC pretreated with heat-killed or live preparations of other gram-positive and gram-negative bacteria such as Streptococcus pyogenes (SP) and Proteus vulgaris (PV). Unlike fMIGWII which is water soluble and protease sensitive, the native antigens extracted from SP and PV, like HAA, were very hydrophobic and proteinase K resistant, presumably reflecting in each case the association of cross-reactive polypeptides with bacterial lipid or phospholipid. Thus, HAA/lemA-immune, H2M3wt-restricted effectors can respond to a variety of formylated peptides and bacterial antigens in vitro. Similar cross-reactions in vivo might have physiologically significant implications.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: C
authors.initials: C
authors.lastname: Nataraj
authors.forename: G R
authors.initials: GR
authors.lastname: Huffman
authors.forename: R J
authors.initials: RJ
authors.lastname: Kurlander
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003429:Cross Reactions; D003602:Cytotoxicity, Immunologic; D006090:Gram-Negative Bacteria / Q000276:immunology*; D006094:Gram-Positive Bacteria / Q000276:immunology*; D008089:Listeria monocytogenes / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D009842:Oligopeptides