Abstract
Hepatitis B virus (HBV) infection remains a worldwide health problem and no eradicative therapy is currently available. Host T cell immune responses have crucial influences on the outcome of HBV infection, however the development of therapeutic vaccines, T cell therapies and the clinical evaluation of HBV-specific T cell responses are hampered markedly by the lack of validated T cell epitopes. This review presented a map of T cell epitopes functionally validated from HBV antigens during the past 33 years; the human leukocyte antigen (HLA) supertypes to present these epitopes, and the methods to screen and identify T cell epitopes. To the best of our knowledge, a total of 205 CD8+ T cell epitopes and 79 CD4+ T cell epitopes have been defined from HBV antigens by cellular functional experiments thus far, but most are restricted to several common HLA supertypes, such as HLA-A0201, A2402, B0702, DR04, and DR12 molecules. Therefore, the currently defined T cell epitope repertoire cannot cover the major populations with HLA diversity in an indicated geographic region. More researches are needed to dissect a more comprehensive map of T cell epitopes, which covers overall HBV proteome and global patients.
Highlights
Hepatitis B virus (HBV) infection still disseminates across the world and causes the most common and fatal liver diseases including acute liver failure, chronic hepatitis, liver cirrhosis (LC), and hepatocellular carcinoma (HCC) [1,2]
Numerous researches have demonstrated the important influence of HBV-specific T cell responses on virus clearance [7], disease progression [8,9,10], antiviral efficacy [11,12], and recurrence [13,14,15], the CD8+ T cells, which act as vital effector cells to kill virus-infected hepatocytes and secret cytokines
A pioneering study focused on all possible peptides of the entire HBV genome and 484 unique human leukocyte antigen (HLA)-A1101-restricted epitopes predicted by NetMHC algorithms were validated using mass cytometry and multiplex peptide-tetramers staining [53]
Summary
Hepatitis B virus (HBV) infection still disseminates across the world and causes the most common and fatal liver diseases including acute liver failure, chronic hepatitis, liver cirrhosis (LC), and hepatocellular carcinoma (HCC) [1,2]. Numerous researches have demonstrated the important influence of HBV-specific T cell responses on virus clearance [7], disease progression [8,9,10], antiviral efficacy [11,12], and recurrence [13,14,15], the CD8+ T cells, which act as vital effector cells to kill virus-infected hepatocytes and secret cytokines. 233 articles were filtered out after abstract and full-text screening, according to the exclusion criteria below: (1) not related to the screening or identification of T cell epitopes; (2) just using in silico prediction or molecular structure bioinformatic analysis rather than satisfactory cell functional experiments, tetramer staining, binding assay, stabilization assay, or immunization; (3) with incomplete information regarding epitopes sequences. 97 articles were analyzed and referenced in this review
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