Effect of antigen-processing efficiency on in vivo T cell response magnitudes.
T lymphocytes eradicate and provide long-term immunity to infections caused by intracellular pathogens. The mechanisms that determine in vivo T cell response sizes are poorly understood. Although it is speculated that the relative processing efficiency of different epitopes determines the hierarchy of T cell responses following immunization, this hypothesis has not been rigorously tested. We therefore mutagenized the secreted p60 Ag of Listeria monocytogenes to alter the efficiency of T cell epitope generation. Ag-processing efficiencies in cells infected with the different L. monocytogenes mutants ranged from one H2-Kd-associated p60 217-225 epitope generated per 15 intracellularly degraded p60 molecules (1/15) to one epitope per 350 degraded p60 molecules (1/350), i.e., a spectrum encompassing a 20-fold range of efficiencies. Mice infected with L. monocytogenes secreting inefficiently processed p60 (1/350) did not mount p60 217-225-specific T cell responses. However, increasing the efficiency of Ag processing by a factor of 5 to 1/70 restored the T cell response size to normal, while further increases in the efficiency of p60 217-225 generation to 1/50, 1/35, and 1/17 did not further augment specific T cell responses. Our studies demonstrate an Ag-processing threshold for in vivo T cell activation. Surprisingly, once this threshold is achieved, further enhancement of Ag-processing efficiency does not enhance the size of T cell responses.
Vijh
S
S
Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520-8022, USA.
Pilip
I M
IM
Pamer
E G
EG
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D013601:T-Lymphocytes / Q000276:immunology*
D000942:Antigens, Bacterial; D017931:DNA Primers