title: Immunization with the HBV core 18-27 epitope elicits CTL responses in humans expressing different HLA-A2 supertype molecules.
abstract: The human leukocyte antigen (HLA)-A2 restricted HBV core 18-27 epitope is immunodominant in the context of HLA-A2.1 and subdominant in the context of the other HLA-A2 supertype molecules, as defined by frequency of recognition by memory cytotoxic T lymphocyte (CTL) responses from acute hepatitis B virus (HBV) patients, and on the basis of its binding affinity to purified HLA molecules in vitro. Herein, we show that immunization with a lipopeptide containing HBV core 18-27 epitope induces CTL responses in patients expressing different HLA-A2 supertype molecules, with indistinguishable frequency and magnitude. No difference in responses was noted between patients expressing either one or two different HLA-A2 supertype molecules. Thus, complexes of HBV core 18-27 bound to different HLA-A2 supertype alleles do not appear to act as altered peptide ligands, and do not cross antagonize CTL responses. These results substantiate the immunological relevance of the HLA supertypes concept, and illustrate its potential usefulness for the development of vaccines.
authors.affiliation: Epimmune, Inc., San Diego, California 92121, USA. blivingston@epimmune.com
authors.forename: B D
authors.initials: BD
authors.lastname: Livingston
authors.forename: C
authors.initials: C
authors.lastname: Crimi
authors.forename: J
authors.initials: J
authors.lastname: Fikes
authors.forename: R W
authors.initials: RW
authors.lastname: Chesnut
authors.forename: J
authors.initials: J
authors.lastname: Sidney
authors.forename: A
authors.initials: A
authors.lastname: Sette
mesh_terms: D000208:Acute Disease; D000483:Alleles; D000595:Amino Acid Sequence; D015789:HLA-A2 Antigen / Q000145:classification / Q000235:genetics / Q000378:metabolism; D006509:Hepatitis B / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D006512:Hepatitis B Core Antigens / Q000235:genetics / Q000378:metabolism; D017325:Hepatitis B Vaccines / Q000494:pharmacology; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007114:Immunization; D016056:Immunodominant Epitopes / Q000235:genetics / Q000378:metabolism; D007156:Immunologic Memory; D066298:In Vitro Techniques; D055666:Lipopeptides; D008074:Lipoproteins / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D011485:Protein Binding; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D015789:HLA-A2 Antigen; D006512:Hepatitis B Core Antigens; D017325:Hepatitis B Vaccines; D016056:Immunodominant Epitopes; D055666:Lipopeptides; D008074:Lipoproteins; D010446:Peptide Fragments; C091434:Theradigm-HBV