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The Journal of Immunology, 1999, 162: 6963-6966.
Copyright © 1999 by The American Association of Immunologists

CUTTING EDGE

Cutting Edge: Silencing Virus-Specific Cytotoxic T Cell-Mediated Immune Recognition by Differential Splicing: A Novel Implication of RNA Processing for Antigen Presentation1

Norbert Kienzle2, Tom B. Sculley, Sonia Greco and Rajiv Khanna

EBV Unit, Queensland Institute of Medical Research, and University of Queensland Joint Oncology Program, Brisbane, Australia

Persistent viruses have developed potent strategies to overcome host immune defenses. In particular, viral interference with Ag presentation by HLA class I molecules can effectively impair the host’s CTL function. Here we provide evidence for a novel aspect of differential splicing on endogenous processing of a latent viral transcript resulting in dominant protein isoforms from which the CTL determinant has been deleted. Consequently, virus-infected cells expressing these isoforms were poorly recognized by CTLs. Molecular analysis revealed that this splicing significantly reduced expression of the viral transcript encoding the relevant epitope to levels below the threshold required for CTL recognition. The importance of splicing was further reinforced by the observation of efficient CTL recognition of target cells expressing a truncated viral transcript that abolished differential splicing. Thus, differential splicing, which is a common mechanism of gene regulation in many pathogens, may unexpectedly interfere with immune recognition.




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