[407] COMPREHENSIVE ANALYSIS OF HBV GENOTYPE-SPECIFIC T CELL RESPONSE IN GENETICALLY DIFFERENT POPULATIONS PERSISTENTLY INFECTED WITH HBV GENOTYPE B OR D

Analysis of HBV-specific T cell response has been limited to few HBV determinants, often restricted to HLA molecules overrepresented in Caucasian and based on genotype D sequence.We initiate a multi-center study to obtain a comprehensive representation of the HBV-specific T cell profile present in Asian and Caucasian patients with persistent HBV genotype D and B infection.Aims of the study are to determine the protein-specific dominance of HBV-specific CD8 and CD4 T cells, to characterize HBV genotype-specific immune responses and evaluate the impact of patient's genetic background and virus genotype on virus-specific cellular immunity.Methods: Two distinct panels of overlapping 15-18 mers peptides covering HBV genotype B and D were synthesized.The genotype specific peptide set was used to asses T cell response in 20 Asian genotype B and 20 Caucasian genotype D persistently infected subjects.Frequency and magnitude of T cell responses was tested directly ex vivo and after in vitro stimulation with gamma-IFN ELISPOT assay and phenotypic analysis for CD4 or CD8 was based on intracellular cytolcine staining.Results: Direct ex vivo HBV-specific T cells were detected in 12 Chinese and 7 Caucasian HBV chronic patients.Polymerase specific T cell response dominates the HBV specific T cell repertoire in both groups of patients.Response to core, envelope and the X protein were rarely detected directly ex vivo.Polymerase response was mainly CD8+ mediated.Responses across the entire polymerase protein with clusters of high immunogenicity in both genotypes were detected.Multi-specific responses with up to 14 different non-overlapping peptides were detected in single subject.Conclusions: HBV-specific T cell responses are detectable in ex vivo analysis patients with different genetic background and diEerent HBV genotypes.The response pattern in chronically infected individuals points towards a dominance against the polymerase protein, a low expressed nonstructural protein in chronic HBV Partner AIDS 14081