Two 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 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.
Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520-8022, USA.
A J
AJ
Sijts
A
A
Neisig
J
J
Neefjes
E G
EG
Pamer
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000276:immunology* / Q000378:metabolism; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism; D001483:Base Sequence; D002999:Clone Cells / Q000276:immunology; D003433:Crosses, Genetic; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006183:H-2 Antigens / Q000276:immunology; D008089:Listeria monocytogenes / Q000201:enzymology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000276:immunology* / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D000939:Epitopes; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D010446:Peptide Fragments; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; D009238:N-Acetylmuramoyl-L-alanine Amidase