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 CD8(+) cells and establishment of lifelong latency, An Epstein-Barr virus (EBV)-l ike infectious mononucleosis (IM) syndrome emerges similar to 3 weeks after infection. In human IM, the majority of T cells in the peripheral blood ar e monoclonal or oligoclonal and are frequently specific for lytic or latent viral epitopes. However, a unique feature of MHV-68-induced IM is a promin ent MHC haplotype-independent expansion of CD8+ T cells, the majority of wh ich utilize V(beta)4 chains in their alpha beta TCR, The ligand driving the V(beta)4 expansion is unknown, but the V beta bias and MHC haplotype indep endence raised the possibility that these cells were responding to a virall y encoded or a virally induced endogenous superantigen (sAg), The aim of th is study was to determine whether this rapidly proliferating subset is comp osed of polyclonally or clonally expanded T cells. Complementarity-determin ing region (CDR)-3 size analysis of V(beta)4(+)CD8(+) cells in infected mic e demonstrated CDR3-restricted expansions in the V(beta)4 family as a whole . More refined analysis demonstrated major distortions in every J(beta) sub family. V-D-J junctional region sequencing indicated that these CDR3 size-r estricted expansions were composed of clonal or oligoclonal populations, Th e sequences were largely unique in individual mice, although evidence for ' public' or highly conserved T cell expansions was also seen between differe nt mice. Taken together with previous studies showing an apparent MHC indep endence, the data suggest that a novel ligand, distinct from conventional s Ag and peptide-MHC, drives proliferation of V(beta)4(+)CD8(+) T cells.