B7-CD28 costimulation unveils the hierarchy of tumor epitopes recognized by major histocompatibility complex class I-restricted CD8+ cytolytic T lymphocytes

Janet V. Johnston, Alison R. Malacko, Mark T. Mizuno, Patrick McGowan, Ingegerd Hellström, Karl Erik Hellström, Hans Marquardt, Lieping Chen

Research output: Contribution to journalArticle

Abstract

Immunization of mice with tumors genetically engineered to express the B7 costimulatory molecules amplifies the antitumor immune response mediated by CD8+ cytolytic T lymphocytes (CTL). In this report, we examined the effect of B7-CD28 costimulation on the hierarchy of tumor epitopes. Using a combination of affinity chromatography/reversed-phase high performance liquid chromatography and CTL cloning, we show that major histocompatibility complex (MHC) class I molecules from EL4 lymphoma cells can present at least six distinct CTL epitopes presented by MHC class 1 molecules. Nevertheless, mice immunized with wild-type B7-negative EL4 cells develop CTL only to one immunodominant epitope. In contrast, immunization with B7-transduced EL4 cells led to not only the amplification of the CTL response to this immunodominant epitope, but also the recognition of five otherwise silent subdominant epitopes. The adoptive transfer of a CTL clone against such a subdominant epitope cured mice bearing EL4 lymphoma growing as an ascites tumor. Thee fact that CTL response can be spread to normally silent epitopes as a result of B7-CD28 costimulation suggests a novel approach to manipulate the hierarchy of CTL epitopes and offers an opportunity to explore novel targets for T cell-mediated cancer therapy.

Original languageEnglish (US)
Pages (from-to)791-800
Number of pages10
JournalJournal of Experimental Medicine
Volume183
Issue number3
DOIs
StatePublished - Mar 1 1996
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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  • Cite this

    Johnston, J. V., Malacko, A. R., Mizuno, M. T., McGowan, P., Hellström, I., Hellström, K. E., Marquardt, H., & Chen, L. (1996). B7-CD28 costimulation unveils the hierarchy of tumor epitopes recognized by major histocompatibility complex class I-restricted CD8+ cytolytic T lymphocytes. Journal of Experimental Medicine, 183(3), 791-800. https://doi.org/10.1084/jem.183.3.791