CTL induction by cross-priming is restricted to immunodominant epitopes

Pavelic, Viktor; Matter, Matthias S; Mumprecht, Sabine; Breyer, Isabel; Ochsenbein, Adrian F (2009). CTL induction by cross-priming is restricted to immunodominant epitopes. European journal of immunology, 39(3), pp. 704-16. Weinheim: Wiley-VCH 10.1002/eji.200838901

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CTL are induced by two pathways, i.e. direct priming, where tumor cells present tumor antigens to naïve specific CTL, and cross-priming, where professional APC cross-present captured tumor antigens to CTL. Here, we examined direct priming versus cross-priming after immunizing (H-2(b) x H-2(d)) F1 mice with either H-2(b) or H-2(d) positive tumor cells transfected with the GP or nucleoprotein (NP) of lymphocytic choriomeningitis virus (LCMV). Cross-priming was observed for the immunodominant epitopes LCMV-gp33 and -np118, although direct induction resulted in higher CTL frequencies. In contrast, CTL specific for the subdominant epitopes LCMV-gp283 or -np396 were induced only if epitopes were presented directly on MHC class I molecules of the immunizing cell. The broader repertoire and the higher CTL frequencies induced after vaccination with haplotype-matched tumor cells resulted in more efficient anti-tumor and antiviral protection. Firstly, our results indicate that certain virus and tumor antigens may not be detected by CD8(+) T cells because of impaired cross-priming. Secondly, efficient cross-priming contributes to the immunodominant nature of a tumor-specific CTL epitope. Thirdly, vaccine strategies using autologous or syngenic antigen-expressing cells induce a broader repertoire of tumor-specific CTL and higher CTL frequencies.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology
UniBE Contributor:	Ochsenbein, Adrian
ISSN:	0014-2980
Publisher:	Wiley-VCH
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 15:11
Last Modified:	05 Dec 2022 14:21
Publisher DOI:	10.1002/eji.200838901
PubMed ID:	19189311
Web of Science ID:	000264683500019
URI:	https://boris.unibe.ch/id/eprint/31382 (FactScience: 195876)