CONSERVED T-CELL RECEPTOR REPERTOIRE IN PRIMARY AND MEMORY CD8 T-CELLRESPONSES TO AN ACUTE VIRAL-INFECTION

Viral infections often induce potent CD8 T cell responses that play a key role in antiviral immunity. After viral clearance, the vast majori ty of the expanded CD8 T cells undergo apoptosis, leaving behind a sta ble number of memory cells. The relationship between the CD8 T cells t hat clear the acute viral infection and the long-lived CD8 memory pool remaining in the individual is not fully understood. To address this issue, we examined the T cell receptor (TCR) repertoire of virus-speci fic CD8 T-cells in the mouse model of infection with lymphocytic chori omeningitis virus (LCMV) using three approaches: (a) in vivo quantitat ive TCR beta chain V segment and complementarity determining region 3 (CDR3) length repertoire analysis by spectratyping (immunoscope); (b) identification of LCMV-specific CD8 T cells with MHC class I tetramers containing viral peptide and costaining with TCR V beta-specific anti bodies; and (c) functional TCR fingerprinting based on recognition of variant peptides. We compared the repertoire of CDS T cells responding to acute primary and secondary LCMV infections, together with that of virus-specific memory T cells in immune mice. Our analysis showed tha t CD8 T cells from several V beta families participated in the anti-LC MV response directed to the dominant cytotoxic T lymphocyte (CTL) epit ope (NP118-126). However, the bulk (similar to 70%) of this CTL respon se was due to three privileged T cell populations systematically expan ding during LCMV infection. Approximately 30% of the response consiste d of V beta 10(+) CDS T cells with a beta chain CDR3 length of nine am ino acids, and 40% consisted of V beta 8.1(+) (beta CDR3 = eight amino acids) and V beta 8.2(+) cells (beta CDR3 = six amino acids). Finally , we showed that the TCR repertoire of the primary antiviral CD8 T cel l response was similar both structurally and functionally to that of t he memory pool and the secondary CD8 T cell effectors. These results s uggest a stochastic selection of memory cells from the pool of CD8 T c ells activated during primary infection.