HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kienzle, N. Articles by Khanna, R. Search for Related Content PubMed PubMed Citation Articles by Kienzle, N. Articles by Khanna, R.

Differential Splicing of Antigen-Encoding RNA Reduces Endogenous Epitope Presentation That Regulates the Expansion and Cytotoxicity of T Cells¹

Norbert Kienzle^2,*, Marion Buck^*, Sharon L. Silins^*, Scott R. Burrows^*, Denis J. Moss^*, Adam Winterhalter, Andrew Brooks and Rajiv Khanna^*

^* EBV Unit, The Queensland Institute of Medical Research and University of Queensland Joint Oncology Program, Brisbane, Queensland, Australia; and Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia

The activation of CTLs is dependent on the recognition of MHC-bound peptide present on the surface of APCs. We give evidence in this study that differential splicing of Ag-encoding RNA can decrease the antigenic dose in APCs and regulate the recall of human memory CTLs. Differential splicing of RNA that encoded an immunodominant HLA-B8-restricted CTL epitope of EBV reduced the functional presentation of this epitope, and consequently the in vitro expansion and activity of CTLs, as measured by MHC/peptide-tetramer staining and cytotoxicity assays. The reduced activity of the stimulated CTLs was not only due to lower numbers of Ag-specific CTLs but, surprisingly, was also characterized by decreased cytotoxicity of the CTLs to target cells presenting limiting amounts of the peptide epitope. As indicated by TCR repertoire analysis, the reduction in CTL activity was not caused by stimulation of distinct populations of TCR clonotypes. This study demonstrates how a common eukaryotic posttranscriptional mechanism of gene regulation can modulate the endogenous presentation of Ag and ultimately contribute to the fine tuning of immunological memory cells, which are important in the fight against pathogens and tumors and in autoimmunity.

This article has been cited by other articles:

				J. Duraiswamy, J. M. Burrows, M. Bharadwaj, S. R. Burrows, L. Cooper, N. Pimtanothai, and R. Khanna Ex Vivo Analysis of T-Cell Responses to Epstein-Barr Virus-Encoded Oncogene Latent Membrane Protein 1 Reveals Highly Conserved Epitope Sequences in Virus Isolates from Diverse Geographic Regions J. Virol., July 1, 2003; 77(13): 7401 - 7410. [Abstract] [Full Text] [PDF]