International Immunology, Vol. 12, No. 8, 1193-1204,
August 2000
© 2000 Japanese Society for Immunology
Murine 
-herpesvirus infection causes Vß4-specific CDR3-restricted clonal expansions within CD8+ peripheral blood T lymphocytes
1 Department of Immunology, St Jude Children's Research Hospital, Memphis, TN 38105, USA
2 Department of Pathology, University of Tennessee, Memphis, TN 38163, USA
3 Epstein–Barr Virus Unit, Queensland Institute of Medical Research and University of Queensland Joint Oncology Program, Brisbane, Queensland 4029, Australia
Correspondence to: M. A. Blackman, Trudeau Institute, 100 Algonquin Avenue, Saranac Lake, NY 12983, USA
Infection of mice with the 
-herpesvirus MHV-68 results in lytic infection in the lung cleared by CD8+ cells and establishment of lifelong latency. An Epstein–Barr virus (EBV)-like infectious mononucleosis (IM) syndrome emerges ~3 weeks after infection. In human IM, the majority of T cells in the peripheral blood are monoclonal or oligoclonal and are frequently specific for lytic or latent viral epitopes. However, a unique feature of MHV-68-induced IM is a prominent MHC haplotype-independent expansion of CD8+ T cells, the majority of which utilize Vß4 chains in their 
ßTCR. The ligand driving the Vß4 expansion is unknown, but the Vß bias and MHC haplotype independence raised the possibility that these cells were responding to a virally encoded or a virally induced endogenous superantigen (sAg). The aim of this study was to determine whether this rapidly proliferating subset is composed of polyclonally or clonally expanded T cells. Complementarity-determining region (CDR)-3 size analysis of Vß4+CD8+ cells in infected mice demonstrated CDR3-restricted expansions in the Vß4 family as a whole. More refined analysis demonstrated major distortions in every Jß subfamily. V–D–J junctional region sequencing indicated that these CDR3 size-restricted expansions were composed of clonal or oligoclonal populations. The sequences were largely unique in individual mice, although evidence for `public' or highly conserved T cell expansions was also seen between different mice. Taken together with previous studies showing an apparent MHC independence, the data suggest that a novel ligand, distinct from conventional sAg and peptide–MHC, drives proliferation of Vß4+CD8+ T cells.
Keywords: MHV-68, superantigens, TCR repertoire
4 Present address: CRC for Asthma, Department of Pathology and Immunology, Monash Medical School, Prahran, Victoria 3118, Australia
5 Present address: Trudeau Institute, Saranac Lake, NY 12983, USA
Transmitting editor: E. Simpson
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. G. Evans, J. M. Moser, L. T. Krug, V. Pozharskaya, A. L. Mora, and S. H. Speck A gammaherpesvirus-secreted activator of V{beta}4+ CD8+ T cells regulates chronic infection and immunopathology J. Exp. Med., March 17, 2008; 205(3): 669 - 684. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Stapler, E. D. Lee, S. A. Selvaraj, A. G. Evans, L. S. Kean, S. H. Speck, C. P. Larsen, and S. Gangappa Expansion of Effector Memory TCR V{beta}4+CD8+ T Cells Is Associated with Latent Infection-Mediated Resistance to Transplantation Tolerance J. Immunol., March 1, 2008; 180(5): 3190 - 3200. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Chen, A. K. Tai, M. Lin, F. Chang, C. Terhorst, and B. T. Huber Signaling Lymphocyte Activation Molecule-Associated Protein Is a Negative Regulator of the CD8 T Cell Response in Mice J. Immunol., August 15, 2005; 175(4): 2212 - 2218. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. I. Macrae, E. J. Usherwood, S. M. Husain, E. Flano, I.-J. Kim, D. L. Woodland, A. A. Nash, M. A. Blackman, J. T. Sample, and J. P. Stewart Murid Herpesvirus 4 Strain 68 M2 Protein Is a B-Cell-Associated Antigen Important for Latency but Not Lymphocytosis J. Virol., September 1, 2003; 77(17): 9700 - 9709. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Finke, S. A. Luther, and H. Acha-Orbea The role of neutralizing antibodies for mouse mammary tumor virus transmission and mammary cancer development PNAS, January 7, 2003; 100(1): 199 - 204. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. T. Belz and P. C. Doherty Virus-Specific and Bystander CD8+ T-Cell Proliferation in the Acute and Persistent Phases of a Gammaherpesvirus Infection J. Virol., May 1, 2001; 75(9): 4435 - 4438. [Abstract] [Full Text]
|
|