A previously unrecognized H-2D(b)-restricted peptide prominent in the primary influenza A virus-specific CD8(+) T-cell response is much less apparentfollowing secondary challenge

Respiratory challenge of H-2(b) mice with an H3N2 influenza A virus causes an acute, transient pneumonitis characterized by the massive infiltration o f CD8(+) T lymphocytes, The inflammatory process monitored by quantitative analysis of lymphocyte populations recovered by bronchoalveolar lavage is g reatly enhanced by prior exposure to an H1N1 virus, with the recall of cros s-reactive CD8(+)-T-cell memory leading to more rapid clearance of the infe ction from the lungs. The predominant epitope recognized by the influenza v irus-specific CD8(+) set has long been thought to be a nucleoprotein (NP366 -374) presented by H-2D(b) ((DNP366)-N-b), This continues to be true for th e secondary H3N2-->H1N1 challenge but can no longer be considered the case for the primary response to either virus, Quantitative analysis based on in tracellular staining for gamma interferon has shown that the polymerase 2 p rotein (PA(224-233)) provides a previously undetected epitope (D(b)PA(224)) that is at least as prominent as (DNP366)-N-b during the first 10 days fol lowing primary exposure to either the H3N2 or H1N1 virus. The response to ( DNP366)-N-b seems to continue for longer, even when infectious virus can no longer be detected, but there is no obvious difference in the prevalence o f memory T cells specific for (DNP366)-N-b and D(b)PA(224). The generalizat ion that the magnitude of the functional memory T-cell pool is a direct con sequence of the clonal burst size during the primary response may no longer be useful, Previous CD8(+) T-cell immunodominance heirarchies defined larg ely by cytotoxic T-lymphocyte assays may need to be revised.