CD4+ T cells specific for a model latency-associated antigen fail to control a gammaherpesvirus in vivo

Smith, Christopher M., Rosa, Gustavo T. L., May, Janet S., Bennett, Neil J., Mouni, Adele M., Belz, Gabrielle T. and Stevenson, Philip G. (2006) CD4+ T cells specific for a model latency-associated antigen fail to control a gammaherpesvirus in vivo. European Journal of Immunology, 36 12: 3186-3197. doi:10.1002/eji.200636164


Author Smith, Christopher M.
Rosa, Gustavo T. L.
May, Janet S.
Bennett, Neil J.
Mouni, Adele M.
Belz, Gabrielle T.
Stevenson, Philip G.
Title CD4+ T cells specific for a model latency-associated antigen fail to control a gammaherpesvirus in vivo
Formatted title
CD4+ T cells specific for a model latency-associated antigen fail to control a gammaherpesvirus in vivo
Journal name European Journal of Immunology   Check publisher's open access policy
ISSN 0014-2980
1521-4141
Publication date 2006-12-01
Year available 2006
Sub-type Article (original research)
DOI 10.1002/eji.200636164
Open Access Status Not yet assessed
Volume 36
Issue 12
Start page 3186
End page 3197
Total pages 12
Place of publication Weinheim, Germany
Publisher Wiley - V C H Verlag GmbH & Co. KGaA
Language eng
Formatted abstract
CD4+ T cells play a major role in containing herpesvirus infections. However, their cellular targets remain poorly defined. In vitro CD4+ T cells have been reported to kill B cells that harbor a latent gammaherpesvirus. We used the B cell-tropic murine gammaherpesvirus-68 (MHV-68) to test whether this also occurred in vivo. MHV-68 that expressed cytoplasmic ovalbumin (OVA) in tandem with its episome maintenance protein, ORF73, stimulated CD8+ T cells specific for the H2-Kb-restricted OVA epitope SIINFEKL and was rapidly eliminated from C57BL/6 (H2b) mice. However, the same virus failed to stimulate CD4+ T cells specific for the I-Ad/I-Ab-restricted OVA323-339 epitope. We overcame any barrier to the MHC class II-restricted presentation of an endogenous epitope by substituting OVA323-339 for the CLIP peptide of the invariant chain (ORF73-IRES-Ii-OVA), again expressed in tandem with ORF73. This virus presented OVA323-339 but showed little or no latency deficit in either BALB/c (H2d) or C57BL/6 mice. Latent antigen-specific CD4+ T cells therefore either failed to recognize key virus-infected cell populations in vivo or lacked the effector functions required to control them.
Keyword CD4+ T cell
Gammaherpesvirus
Immune evasion
Latency
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID G0400427
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Chemistry and Molecular Biosciences
 
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