Murine gamma-herpesvirus infection causes V(beta)4-specific CDR3-restricted clonal expansions within CD8(+) peripheral blood T lymphocytes.
Infection of mice with the gamma-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 approximately 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 V(beta)4 chains in their alphabetaTCR. The ligand driving the V(beta)4 expansion is unknown, but the V(beta) 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 V(beta)4(+)CD8(+) cells in infected mice demonstrated CDR3-restricted expansions in the V(beta)4 family as a whole. More refined analysis demonstrated major distortions in every J(beta) 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 V(beta)4(+)CD8(+) T cells.
Department of Immunology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
C L
CL
Hardy
S L
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Silins
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Woodland
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Blackman
D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells / Q000276:immunology; D018142:Gammaherpesvirinae / Q000276:immunology*; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006566:Herpesviridae Infections / Q000276:immunology*; D007244:Infectious Mononucleosis / Q000276:immunology* / Q000821:virology; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D011024:Pneumonia, Viral / Q000276:immunology* / Q000821:virology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D016415:Sequence Alignment; D017385:Sequence Homology; D018089:Superantigens / Q000276:immunology; D017735:Virus Latency
D000956:Antigens, Viral; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens