Comparative analysis of HLA restriction and cytokine production in hepatitis B surface antigen-specific T cells from low- and high-antibody responders in vaccinated humans

It is well known that individuals with low, or lack of, antibody production in response to hepatitis B surface antigen (HBsAg) exist in the human popu lation. We have previously reported that HLA class I and class II genes are both involved in antibody production to HBsAg, and that specific alleles o f HLA are associated with low and high antibody production. To elucidate fu rther the mechanisms by which the diversity of antibody production to HBsAg is generated in humans, a total of 146 T-cell clones specific for HBsAg we re produced from six healthy vaccinees (three low- and three high-antibody responders) and were examined for cytokine production and HLA restriction. It was found that the majority of the T-cell clones from the low-antibody r esponders were Th1- or Th0-like T cells (62% or 19%, respectively), whereas the majority of T-cell clones from the high-antibody responders were Th2-l ike T cells (77%), suggesting predominant expansion of Th1/Th0- and Th2-lik e T cells specific for HBsAg in the low- and high-antibody responders, resp ectively. This is the first evidence that the diversity of the response to HBsAg in humans is controlled by the activation of functionally distinct CD 4(+) T-cell subsets, i.e., Th0, Th1, or Th2 T cells.