The Induction of Virus-Specific CTL as a Function of Increasing Epitope Expression: Responses Rise Steadily Until Excessively High Levels of Epitope Are Attained

• Published in: The Journal of immunology (1950) Vol. 163; no. 7; pp. 3735 - 3745
• Main Authors: Wherry, E. John, Puorro, Kristin A, Porgador, Angel, Eisenlohr, Laurence C
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.10.1999
• Subjects: Animals; Antigens, Surface - metabolism; Antigens, Viral - biosynthesis; Antigens, Viral - genetics; Antigens, Viral - immunology; Cytotoxicity, Immunologic; Dose-Response Relationship, Immunologic; Egg Proteins - genetics; Egg Proteins - immunology; Epitopes, T-Lymphocyte - biosynthesis; Epitopes, T-Lymphocyte - genetics; Epitopes, T-Lymphocyte - metabolism; Female; Hybridomas; Influenza A virus - immunology; L Cells (Cell Line); Lymphocyte Activation; Lymphocyte Count; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Nucleoproteins - biosynthesis; Nucleoproteins - genetics; Nucleoproteins - immunology; Ovalbumin - genetics; Ovalbumin - immunology; Peptide Fragments; RNA-Binding Proteins; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - metabolism; T-Lymphocytes, Cytotoxic - virology; Vaccinia virus; Vaccinia virus - genetics; Vaccinia virus - immunology; Viral Core Proteins - biosynthesis; Viral Core Proteins - genetics; Viral Core Proteins - immunology; Viral Vaccines - genetics; Viral Vaccines - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.163.7.3735

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.