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

Oh, SK and Hodge, JW and Ahlers, JD and Burke, DS and Schlom, J and Berzofsky, JA (2003) Selective induction of high avidity CTL by altering the balance of signals from APC. Journal of Immunology, 170 (5). 2523 - 2530. ISSN 0022-1767

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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.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Oh, SK
Hodge, JW
Ahlers, JD
Burke, DSdonburke@pitt.eduDONBURKE
Schlom, J
Berzofsky, JA
Centers: Other Centers, Institutes, or Units > Center for Vaccine Research
Date: 1 March 2003
Date Type: Publication
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Journal or Publication Title: Journal of Immunology
Volume: 170
Number: 5
Page Range: 2523 - 2530
DOI or Unique Handle: 10.4049/jimmunol.170.5.2523
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Epidemiology
Refereed: Yes
ISSN: 0022-1767
Date Deposited: 08 May 2015 15:11
Last Modified: 02 Feb 2019 16:57
URI: http://d-scholarship.pitt.edu/id/eprint/24326

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