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.
Gray
Peter M
PM
Department of Microbiology and Immunology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
Parks
Griffith D
GD
Alexander-Miller
Martha A
MA
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology* / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D002460:Cell Line; D006207:Half-Life; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D045402:Parainfluenza Virus 5 / Q000276:immunology* / Q000378:metabolism; D010750:Phosphoproteins / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D016601:RNA-Binding Proteins; D019351:Rubulavirus Infections / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D025801:Ubiquitin / Q000378:metabolism; D014764:Viral Proteins / Q000276:immunology / Q000378:metabolism
D000956:Antigens, Viral; C097018:P protein, Simian parainfluenza virus 5; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D025801:Ubiquitin; D014764:Viral Proteins