Modulation of CD8+ T cell avidity by increasing the turnover of viral antigen during infection

The increased potency of high avidity CD8(+) T cells for the clearance of viral infections has been well documented. We have previously reported the novel finding that intranasal infection with the paramyxovirus SV5 induces a CD8(+) T cell response to the SV5 P protein that is almost exclusively of high avidity. Based on our results that the level of peptide presentation is a critical factor in the selective expansion of high versus low avidity cells in vitro, we hypothesized that the avidity of the anti-viral response generated in vivo could be altered by increasing the turnover of the P protein during viral infection through linkage to ubiquitin (UbP). Infection with a virus expressing UbP (VV-UbP) elicited a significant increase in low avidity cells in both BALB/c and C3H mice compared to the almost exclusively high avidity response elicited by VV-P. Our results are the first demonstration of the control of avidity during the antiviral response through an engineered change to a viral antigen. The implications of our findings for vaccine development are discussed. (c) 2004 Elsevier Inc. All rights reserved.