The immunodominant L~d-restricted T cell response to hepatitis B surface antigen (HBsAg) efficiently suppresses T cell priming tomultiple D~d-,K~d-,and K~b-restricted HBsAg epitopes

摘要

MHC-I-restricted CTL responses of H-2~d(L~(d+) or L~(d-)) and F-1H-2~(dxb) mice to hepatitis B surface Ag(ABsAg) are primed by either DNA vaccines or ABsAg particles.The D~d/S_(201-209) and K~d/S_(199-208) epitopes are generated by processing endogenous HBsAg;the K~b/S_(208-215) epitope is generated by processing exogenous HBsAg;and the L~d/S_(28-29) epitope is generated by exogenous as well as endogenous processing of HBsAg.DNA vaccination primed high numbers of CTL specific for the L~d/S_(29-29) HBsAg epitope,low numbers of CTL specific for the D~d/S_(201-209) or K~d/S_(199-208) HBsAg epitopes in BALB/c mice,and high numbers of D~d/S_(201-209)-and K~d/S_(199-208)-specific CTL in congenic H-2~d/L~(d-) dm2 mice.In F_1~(dxb) mice,the K~d-,D~d-,and K~b-resricted CTL responses to HBsAg were strikingly suppressed in the presence but efficiently elicited in the absence of L~d/S_(28-29)-specific CTL.Once primed,the K~d- and D~d-restricted CTL responses to HBsAg were resistant to suppression by immunodominant L~d/S_(28-29)-specific CTL.The L~d-restricted immunodominant CTL reactivity to HBsAg can thus suppress priming to multiple alternative epitopes of HBsAg,independent of the processing pathway that generates the epitope,of the background of the mouse strain used,and of the presence/absence of different allelic variants of the K and D MHC class I molecules.