A novel CDS-independent high-avidity cytotoxic T-lymphocyte response directed against an epitope in the phosphoprotein of the paramyxovirus simian virus 5

Adoptive transfer studies have shown that cytotoxic T lymphocytes (CTL) of high avidity, capable of recognizing low levels of peptide-MHC I molecules, are more efficient at reducing viral titers than are low-avidity CTL, thus establishing CTL avidity as a critical parameter for the ability of a CTL to clear virus in vivo. It has been well documented that CTL of high avidit y are relatively CD8 independent, whereas low-avidity CTL require CD8 engag ement in order to become activated. In this study we have analyzed the anti viral CTL response elicited following infection with the paramyxovirus simi an virus 5 (SV5). We have identified the immunodominant and subdominant CTL responses and subsequently assessed the avidity of these responses by thei r CD8 dependence. This is the first study in which the relationship between immunodominance and CTL avidity has been investigated. The immunodominant response was directed against an epitope present in the viral M protein, an d subdominant responses were directed against epitopes present in the P, F, and HN proteins. Similarly to other CTL responses we have analyzed, the im munodominant response and the subdominant F and HN responses were comprised of both high- and low-avidity CTL. However, the subdominant response direc ted against the epitope present in the P protein is novel, as it is exclusi vely high avidity. This high-avidity response is independent of both the ro ute of infection and expression by recombinant SV5. A further understanding of the inherent properties of P that elicit only high-avidity CTL may allo w for the design of more efficacious vaccine vectors that preferentially el icit high-avidity CTL in vivo.