H2M3wt-restricted, Listeria monocytogenes-immune CD8 T cells respond to multiple formylated peptides and to a variety of gram-positive and gram- negative bacteria

A subset of H2M3wt-restricted, Listeria monocytogenes (LM)-immune CD8effectors recognize antigen-presenting cells (APC) preincubated withheat-killed LM. The responsible product, which we have previouslydesignated heat-killed Listeria-associated antigen (HAA), is extremelyhydrophobic and resistant to proteolytic degradation. Despite the proteaseresistance of HAA, we now report that HAA-immune clones are uniformlyresponsive to fMIGWII, a formylated oligopeptide derived from the recentlydescribed LM product, lemA. While fMIGWII was by far the most potentpeptide tested, over half our clones also responded to the LM-derivedpeptide fMIVII and cross-reactive responses to two other unrelatedformylated peptides at concentrations of <1 microM were frequentlyobserved. One of these peptides (fBlaZ) did not share any amino acid incommon with fMIGWII except N-formyl methionine at position 1. Unformylatedvariants of the same peptides were inactive. HAA-immune CD8 cells alsoresponded in an H2M3wt-restricted manner to APC pretreated with heat-killedor live preparations of other gram- positive and gram-negative bacteriasuch as Streptococcus pyogenes (SP) and Proteus vulgaris (PV). UnlikefMIGWII which is water soluble and protease sensitive, the native antigensextracted from SP and PV, like HAA, were very hydrophobic and proteinase Kresistant, presumably reflecting in each case the association ofcross-reactive polypeptides with bacterial lipid or phospholipid. Thus,HAA/lemA-immune, H2M3wt- restricted effectors can respond to a variety offormylated peptides and bacterial antigens in vitro. Similarcross-reactions in vivo might have physiologically significantimplications.