CD4(+) T cells specific for a model latency-associated antigen fail to control a gammaherpesvirus in vivo
- Author(s)
- Smith, CM; Rosa, GTL; May, JS; Bennett, NJ; Mount, AM; Belz, GT; Stevenson, PG;
- Details
- Publication Year 2006-12,Volume 36,Issue #12,Page 3186-3197
- Journal Title
- EUROPEAN JOURNAL OF IMMUNOLOGY
- Publication Type
- Journal Article
- 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 ovalburnin (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.
- Publisher
- WILEY-V C H VERLAG GMBH
- Keywords
- EPSTEIN-BARR-VIRUS; GAMMA-HERPESVIRUS LATENCY; PEPTIDE-LOADING COMPLEX; MEMORY B-CELLS; MURINE GAMMAHERPESVIRUS-68; NUCLEAR ANTIGEN-1; IMMUNE EVASION; MEDIATED CONTROL; DEFICIENT MICE; HELPER-CELLS
- Publisher's Version
- https://doi.org/10.1002/eji.200636164
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- Refer to copyright notice on published article.
Creation Date: 2006-12-01 12:00:00