CYTOTOXIC T-CELLS SPECIFIC FOR A SINGLE PEPTIDE ON THE M2 PROTEIN OF RESPIRATORY SYNCYTIAL VIRUS ARE THE SOLE MEDIATORS OF RESISTANCE INDUCED BY IMMUNIZATION WITH M2 ENCODED BY A RECOMBINANT VACCINIA VIRUS

We have studied the immunobiology of respiratory syncytial virus (RSV), a major cause of respiratory tract morbidity in children. As part of these studies, it was previously found that immunization of BALB/c (H-2(d)) mice with a recombinant vaccinia virus (rVV) which encoded the M2 protein of RSV provided complete protection against infection with RSV. This protection was transient and associated with M2-specific CD8(+) T-cell (T-CD8+) responses. In this study, we used two approaches to demonstrate that expression of an H-2K(d)-restricted nonameric peptide (Ser Tyr Ile Gly Ser Ile Asn Asn Ile) corresponding to M2 residues 82 to 90 is necessary and sufficient to induce protective T-CD8+ responses. First, infection of mice with an rVV which encoded the peptide M2(Met82-90) induced levels of primary pulmonary T-CD8+ and resistance to RSV challenge equivalent to that induced by infection with an rVV which expressed the complete M2 protein. Second, elimination of peptide binding to K-d by the replacement of Tyr with Arg at amino acid position 83 of the full-length protein completely abrogated the ability of an rVV-expressing full-length M2 to induce either M2-specific T-CD8+ responses or resistance to RSV infection. These findings demonstrate that the M2(82-90) peptide is the sole determinant of immunity induced in BALB/c mice by the M2 protein and that a remarkably high level of transient resistance to infection with pulmonary virus is associated with T-CD8+ responses to a single determinant.