The Journal of Immunology, Vol 156, Issue 2 683-692, Copyright © 1996 by American Association of Immunologists

ARTICLES

Two Listeria monocytogenes CTL epitopes are processed from the same antigen with different efficiencies

AJ Sijts, A Neisig, J Neefjes and EG Pamer
Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520-8022, USA.

Listeria monocytogenes is an intracellular bacterium that elicits MHC class I-restricted CTL in infected mice. A major CTL specificity is the nonamer peptide p60 217-225, which is derived from the bacterial murein hydrolase p60 and presented by the H-2Kd MHC class I molecule. In this report, we identify a second H-2Kd presented peptide, encompassing residues 449-457 of p60, that is detected by L. monocytogenes-specific CTL. Both p60-derived CTL epitopes are good competitors for H-2Kd binding and TAP (transporter associated with Ag processing) transport. CTL clone WP11.12 lyses L. monocytogenes infected cells and recognizes naturally processed p60 449-457 acid eluted from L. monocytogenes- infected macrophages. Although both epitopes derive from the same Ag and bind the same allelic form of MHC class I, quantitative analysis reveals that the amount of p60 449-457 in infected cells is approximately 10-fold greater than the amount of p60 217-225. Shuffling p60 217-225 into position 449-457 decreases its processing efficiency, indicating that the large number of p60 449-457 epitopes cannot be entirely attributed to epitope-flanking sequences. Our findings indicate that CTL 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.

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