T cell responses to respiratory syncytial virus fusion and attachment proteins in human peripheral blood mononuclear cells

The cellular immune response to respiratory syncytial virus (RSV) is considered important in both protection and immunopathogenesis. We have studied the HLA class I- and class II-restricted T cell responses to RSV fusion (F) and attachment (G) proteins in peripheral blood mononuclear cells (PBMCs) obtained from healthy young adults. PBMCs were stimulated with autologous cells infected with recombinant modified vaccinia virus Ankara (rMVA) expressing RSV F (rMVA-F) or G (rMVA-G). In rMVA-F-stimulated bulk cultures F-specific CD4+and CD8+T cell responses were demonstrated, whereas in rMVA-G-stimulated cultures only G-specific CD4+T cell responses were detected. Using a set of overlapping peptides spanning the F protein, a number of the F-specific T cell responses could be mapped to different antigenic regions, whereas for the G protein only CD4+T cell responses recognizing the central conserved domain could be detected. These results suggest that the RSV glycoprotein-specific T cell response is directed to a number of different epitopes. Further studies must be performed to confirm the apparent inability of the RSV G protein to induce CD8+T cell responses. The rMVA-based in vitro stimulation protocol will be useful to define protein-specific T cell responses in different viral systems.

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