The induction of virus-specific CTL as a function of increasing epitope expression: responses rise steadily until excessively high levels of epitope are attained.
The role of epitope expression levels in CD8+ T cell priming has been controversial. Yet this parameter is of great importance in the design of rational approaches to optimize CTL responses to a variety of pathogens. In this paper we examine the influence of epitope production on CD8+ T cell priming by exploiting a system that allows a 200-fold range of cell surface epitope expression in vitro with a fixed dose of vaccinia virus. Our results demonstrate that, with the exception of a notable decline at the highest level of epitope, the magnitude of the responding CTL population generated in vivo following equivalent viral infections is essentially proportional to epitope density.
Wherry
E J
EJ
Department of Microbiology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Puorro
K A
KA
Porgador
A
A
Eisenlohr
L C
LC
D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D000956:Antigens, Viral / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D004306:Dose-Response Relationship, Immunologic; D004527:Egg Proteins / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D005260:Female; D006825:Hybridomas; D009980:Influenza A virus / Q000276:immunology; D007739:L Cells; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D010446:Peptide Fragments; D016601:RNA-Binding Proteins; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology; D014758:Viral Core Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology
D000954:Antigens, Surface; D000956:Antigens, Viral; D004527:Egg Proteins; D018984:Epitopes, T-Lymphocyte; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; C110366:OVA-8; D010446:Peptide Fragments; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins; D014765:Viral Vaccines; D010047:Ovalbumin