Limiting-dilution analysis of the HLA restriction of anti-Epstein-Barr virus-specific cytolytic T lymphocytes.

Human Epstein-Barr virus (EBV) specific cytotoxic T lymphocytes (CTL) play an important role in maintaining the virus/host equilibrium during persistent infections. We analysed precursors of anti-EBV CTL by the limiting-dilution technique. Seven healthy EBV-seropositive and two EBV-seronegative donors were tested. All the donors seropositive for EBV gave clear-cut positive results, and it was remarkable that the frequency of CTL precursors (CTLp) observed was much higher than that reported for other viruses. In contrast, in the seronegative donors the frequency of CTLp was undetectable. The CTLp were derived from the CD4-CD8+ population only, although EBV-specific CD4+ cytolytic T cell clones have been described. A study of the HLA restriction showed that some HLA-A or HLA-B antigens can function as preferential restricting molecules, but that CTLp restricted by the other HLA-A or HLA-B molecules also exist. However, the dominant population of CTL present in primary responses is sometimes different from that of long term cell lines established from the same donor.