CD4+ T cells specific for a model latency-associated antigen fail to control a gammaherpesvirus in vivo.
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.
Smith
Christopher M
CM
Division of Virology, Department of Pathology, University of Cambridge, Cambridge, UK.
Rosa
Gustavo T L
GT
May
Janet S
JS
Bennett
Neil J
NJ
Mount
Adele M
AM
Belz
Gabrielle T
GT
Stevenson
Philip G
PG
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006566:Herpesviridae Infections / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D041681:NIH 3T3 Cells; D018144:Rhadinovirus / Q000276:immunology*; D014412:Tumor Virus Infections / Q000276:immunology*; D017735:Virus Latency / Q000276:immunology*
D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte