Recognition of respiratory syncytial virus fusion protein by mouse cytotoxic T cell clones and a human cytotoxic T cell line.

Two mouse cytotoxic T cell (Tc) clones, D5 and H11a, with specificity for the respiratory syncytial virus (RSV) fusion protein (F) were derived from BALB/c mice primed intranasally (i.n.) with RSV (A2 strain). These clones possessed essentially the same characteristics, and only clone H11a is described here. Tc clone H11a lysed target cells infected with a recombinant vaccinia virus (VV) expressing the RSV F gene, and similar target cells infected with RSV strains Long, 8/60, or 18537. In addition, two RSV-specific mouse Tc lines are described, from BALB/c mice primed i.n. with RSV A2 (Tc line MJC-A2), or intraperitoneally with a VV-RSV F gene recombinant (Tc line MJC-F). Tc line MJC-A2 was of unknown antigen specificity, failing to lyse targets infected with recombinant VVs expressing the RSV nucleoprotein (N), large glycoprotein, F, 1A, 1C, or partial matrix protein (amino acid residues 88 to 257) genes. MJC-A2 Tc were cross-reactive for all strains of RSV tested. In contrast, the F-specific MJC-F Tc showed a marked degree of RSV strain specificity, efficiently lysing targets infected with RSV Long or A2 strains, but showing greatly reduced lysis of targets infected with RSV 8/60 or 18537 strains. An anti-RSV human Tc line, IH.K2, also recognized the fusion protein. IH.K2 Tc efficiently lysed autologous Epstein-Barr virus-transformed B cells (BCL) persistently infected with RSV A2 and BCL infected with a VV-RSV F gene recombinant. IH.K2 function was not exclusively RSV F-specific, however, as these cells also lysed autologous BCL infected with a VV-RSV N gene recombinant. These data show that the RSV fusion protein is a target antigen for anti-RSV Tc following infection of mice and humans, and that the F-specific Tc repertoire in mice can be influenced by the method and route of priming.