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

Eur J Immunol. 2006 Dec;36(12):3186-97. doi: 10.1002/eji.200636164.


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-K(b)-restricted OVA epitope SIINFEKL and was rapidly eliminated from C57BL/6 (H2(b)) mice. However, the same virus failed to stimulate CD4(+) T cells specific for the I-A(d)/I-A(b)-restricted OVA(323-339) epitope. We overcame any barrier to the MHC class II-restricted presentation of an endogenous epitope by substituting OVA(323-339) for the CLIP peptide of the invariant chain (ORF73-IRES-Ii-OVA), again expressed in tandem with ORF73. This virus presented OVA(323-339) but showed little or no latency deficit in either BALB/c (H2(d)) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Viral / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Line
  • Cells, Cultured
  • Epitopes, T-Lymphocyte / immunology*
  • Herpesviridae Infections / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Models, Biological
  • NIH 3T3 Cells
  • Rhadinovirus / immunology*
  • Tumor Virus Infections / immunology*
  • Virus Latency / immunology*


  • Antigens, Viral
  • Epitopes, T-Lymphocyte