Primary
infection with virus can stimulate a vigorous cytotoxic T cell response. The magnitude of the
antigen-specific component versus the bystander component of a primary T cell response remains controversial. In this study, we have used tetrameric major histocompatibility complex-
peptide complexes to directly visualize
antigen-specific cluster of differentration (CD)8+ T cells during the primary immune response to Epstein-Barr virus (
EBV) infection in humans. We show that massive expansion of activated,
antigen-specific T cells occurs during the primary response to this virus. In one individual, T cells specific for a single EBV
epitope comprised 44% of the total CD8+ T cells within peripheral blood. The majority of the
antigen-specific cells had an activated/memory phenotype, with expression of human histocompatibility leukocyte
antigen (
HLA) DR, CD38, and CD45RO, downregulation of CD62 leukocyte (CD62L), and low levels of expression of CD45RA. After recovery from AIM, the frequency of
antigen-specific T cells fell in most donors studied, although populations of
antigen-specific cells continued to be easily detectable for at least 3 yr.