2 LISTERIA-MONOCYTOGENES CTL EPITOPES ARE PROCESSED FROM THE SAME ANTIGEN WITH DIFFERENT EFFICIENCIES

Listeria monocytogenes is an intracellular bacterium that elicits MHC class I-restricted CTL in infected mice, A major CTL specificity is th e nonamer peptide p60 217-225, which is derived from the bacterial mur ein hydrolase p60 and presented by the H-2K(d) MHC class I molecule, I n this report, we identify a second H-2K(d) presented peptide, encompa ssing residues 449-357 of p60, that is detected by L, monocytogenes-sp ecific CTL, Both p60-derived CTL epitopes are good competitors for H-2 K(d) binding and TAP (transporter associated with Ag processing) trans port, CTL clone WP11.12 lyses L. monocytogenes infected cells and reco gnizes naturally processed p60 449-457 acid eluted from L. monocytogen es-infected macrophages, Although both epitopes derive from the same A g and bind the same allelic form of MHC class I, quantitative analysis reveals that the amount of p60 449-457 in infected cells is approxima tely 10-fold greater than the amount of p60 217-225, Shuffling p60 217 -225 into position 449-457 decreases its processing efficiency, indica ting that the large number of p60 449-457 epitopes cannot be entirely attributed to epitope-flanking sequences, Our findings indicate that C TL epitopes can be processed from Ags with markedly different kinetics and efficiencies, Intrinsic qualities of an epitope and its location within a protein influence the efficiency of Ag processing.