Efficiency of MHC class I antigen processing: a quantitative analysis.
Listeria monocytogenes is an intracellular pathogen that secretes proteins into host cell cytosol. One such protein, the murein hydrolase p60, is processed by the host cell into the nonamer peptide p60 217-225 and presented to cytotoxic T lymphocytes by the H-2Kd MHC class I molecule. Using strains of L. monocytogenes that secrete different amounts of p60, we show that the rate of p60 217-225 production is proportional to the quantity of intracellular antigen. The appearance of p60 217-225 is coupled to the degradation of newly synthesized p60. By accounting for the rate of intracellular antigen secretion and degradation, we estimate that approximately 35 p60 molecules are degraded to produce one p60 217-225 epitope. These findings provide an estimate of the efficiency of antigen processing and shed light on the capacity of the MHC class I antigen processing pathway to accommodate foreign antigens.
Villanueva
M S
MS
Section of Infectious Diseases, Yale School of Medicine, New Haven, Connecticut 06520-8022.
Fischer
P
P
Feen
K
K
Pamer
E G
EG
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000942:Antigens, Bacterial / Q000096:biosynthesis / Q000276:immunology*; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000276:immunology*; D001483:Base Sequence; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D006183:H-2 Antigens / Q000276:immunology*; D008089:Listeria monocytogenes / Q000254:growth & development / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
C078516:60 kDa protein, Listeria monocytogenes; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D000939:Epitopes; D006183:H-2 Antigens