Selective induction of high avidity CTL by altering the balance of signals from APC

SangKon Oh, James W. Hodge, Jeffrey D. Ahlers, Donald S. Burke, Jeffrey Schlom, Jay A. Berzofsky

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

High avidity CTL are most effective at clearing viruses and cancer cells. Therefore, understanding the mechanisms involved in induction of high avidity CTL is critical for effective vaccines. However, no vaccine approach to selectively induce high avidity CTL in vivo has been discovered. In a new approach, signals from MHC class I (signal 1) and costimulatory molecules (signal 2) were adjusted by varying Ag dose and by use of recombinant poxvirus expressing a triad of costimulatory molecules (B7-1, ICAM-1, and LFA-3), respectively. Independent of CTL avidity, a strong signal 1 resulted in an increased frequency of CD8+ CTL. However, a strong signal 2 was necessary for the induction of high avidity CD8+ CTL that killed target cells more efficiently, and signal 2 played a more crucial role in the absence of a strong signal 1. Only CTL induced with strong signal 2 killed tumor cells endogenously expressing low levels of Ag. Signal 2 contributed to the induction of high avidity CD8+ CTL in both primary and secondary responses. Thus, although signal 2 has been known to increase the quantity of CTL response, in this study we show that it also improves the quality of CTL response. Our data also suggested that dendritic cells play an important role in induction of high avidity CD8+ CTL in vivo. This strategy to selectively induce higher avidity CTL may lead to more effective vaccines for viruses and cancer.

Original languageEnglish (US)
Pages (from-to)2523-2530
Number of pages8
JournalJournal of Immunology
Volume170
Issue number5
DOIs
StatePublished - Mar 1 2003
Externally publishedYes

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Vaccines
CD80 Antigens
CD58 Antigens
Viruses
Poxviridae
Cancer Vaccines
Intercellular Adhesion Molecule-1
Dendritic Cells
Neoplasms

ASJC Scopus subject areas

  • Immunology

Cite this

Oh, S., Hodge, J. W., Ahlers, J. D., Burke, D. S., Schlom, J., & Berzofsky, J. A. (2003). Selective induction of high avidity CTL by altering the balance of signals from APC. Journal of Immunology, 170(5), 2523-2530. https://doi.org/10.4049/jimmunol.170.5.2523

Selective induction of high avidity CTL by altering the balance of signals from APC. / Oh, SangKon; Hodge, James W.; Ahlers, Jeffrey D.; Burke, Donald S.; Schlom, Jeffrey; Berzofsky, Jay A.

In: Journal of Immunology, Vol. 170, No. 5, 01.03.2003, p. 2523-2530.

Research output: Contribution to journalArticle

Oh, S, Hodge, JW, Ahlers, JD, Burke, DS, Schlom, J & Berzofsky, JA 2003, 'Selective induction of high avidity CTL by altering the balance of signals from APC', Journal of Immunology, vol. 170, no. 5, pp. 2523-2530. https://doi.org/10.4049/jimmunol.170.5.2523
Oh, SangKon ; Hodge, James W. ; Ahlers, Jeffrey D. ; Burke, Donald S. ; Schlom, Jeffrey ; Berzofsky, Jay A. / Selective induction of high avidity CTL by altering the balance of signals from APC. In: Journal of Immunology. 2003 ; Vol. 170, No. 5. pp. 2523-2530.
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