The PreS1 Antigen of Hepatitis B Virus is Highly Immunogenic at the T Cell Level in Man

Overview

Journal J Clin Invest

Specialty General Medicine

Date 1989 Oct 1

PMID 2529268

Citations 15

Authors

C Ferrari

A Penna

A Bertoletti

A Cavalli

A Valli

C Schianchi

F Fiaccadori

Affiliations

Soon will be listed here.

Abstract

14 hepatitis B vaccine recipients who showed high titers of anti-hepatitis B surface antibodies in serum after booster immunization with a polyvalent hepatitis B surface antigen vaccine that contained trace amounts of hepatitis B virus (HBV) preS1 and preS2 envelope antigens were studied for their in vitro T cell response to these antigens. All 14 subjects displayed a significant proliferative T cell response to the S/p25 envelope region encoded polypeptide; 8 also responded to preS1, while only 1 showed a significant level of T cell proliferation to preS2. Limiting dilution analysis demonstrated that the frequency of preS-specific T cells in two of these vaccine recipients was higher than that of S/p25-specific T cells. T cell cloning was then performed and a total of 29 HBV envelope antigen-reactive CD4+ cloned lines were generated from two preS-responsive vaccines. 21 of these lines were S/p25 specific, 7 preS1 specific, and 1 preS2 specific. Taken together, all these results suggest that the preS1 antigen may function as a strong T cell immunogen in man.

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References

Steward M, Sisley B, Stanley C, Brown S, Howard C . Immunity to hepatitis B: analysis of antibody and cellular responses in recipients of a plasma-derived vaccine using synthetic peptides mimicking S and pre-S regions. Clin Exp Immunol. 1988; 71(1):19-25. PMC: 1541641. View

Brett S, Kingston A, Colston M . Limiting dilution analysis of the human T cell response to mycobacterial antigens from BCG vaccinated individuals and leprosy patients. Clin Exp Immunol. 1987; 68(3):510-20. PMC: 1542738. View

Jin Y, Shih W, Berkower I . Human T cell response to the surface antigen of hepatitis B virus (HBsAg). Endosomal and nonendosomal processing pathways are accessible to both endogenous and exogenous antigen. J Exp Med. 1988; 168(1):293-306. PMC: 2188961. DOI: 10.1084/jem.168.1.293. View

Milich D, Thornton G, Neurath A, Kent S, Michel M, Tiollais P . Enhanced immunogenicity of the pre-S region of hepatitis B surface antigen. Science. 1985; 228(4704):1195-9. DOI: 10.1126/science.2408336. View

Neurath A, Kent S, Strick N, Stark D, Sproul P . Genetic restriction of immune responsiveness to synthetic peptides corresponding to sequences in the pre-S region of the hepatitis B virus (HBV) envelope gene. J Med Virol. 1985; 17(2):119-25. DOI: 10.1002/jmv.1890170204. View

Ohnuma H, Takahashi K, Kishimoto S, Machida A, Imai M, Mishiro S . Large hepatitis B surface antigen polypeptides of Dane particles with the receptor for polymerized human serum albumin. Gastroenterology. 1986; 90(3):695-701. DOI: 10.1016/0016-5085(86)91125-x. View

Neurath A, Kent S, Strick N . Detection of antiviral antibodies with predetermined specificity using synthetic peptide--beta-lactamase conjugates: application to antibodies specific for the preS region of the hepatitis B virus envelope proteins. J Gen Virol. 1986; 67 ( Pt 3):453-61. DOI: 10.1099/0022-1317-67-3-453. View

Neurath A, Strick N, Kent S, Offensperger W, Wahl S, Christman J . Enzyme-linked immunoassay of pre-S gene-coded sequences in hepatitis B vaccines. J Virol Methods. 1985; 12(3-4):185-92. DOI: 10.1016/0166-0934(85)90128-4. View

Sohnle P . Lymphocyte transformation and the number of antigen-responsive cells in humans. J Immunol. 1981; 127(2):612-5. View

10.

Koziol J, Ferrari C, Chisari F . Evaluation of monoclonality of cell lines from sequential dilution assays. J Immunol Methods. 1987; 105(1):139-43. DOI: 10.1016/0022-1759(87)90424-8. View

11.

Kniskern P, Hagopian A, Burke P, Dunn N, Emini E, MILLER W . A candidate vaccine for hepatitis B containing the complete viral surface protein. Hepatology. 1988; 8(1):82-7. DOI: 10.1002/hep.1840080117. View

12.

Celis E, Ou D, Otvos Jr L . Recognition of hepatitis B surface antigen by human T lymphocytes. Proliferative and cytotoxic responses to a major antigenic determinant defined by synthetic peptides. J Immunol. 1988; 140(6):1808-15. View

13.

van Oers M, Pinkster J, Zeijlemaker W . Quantification of antigen-reactive cells among human T lymphocytes. Eur J Immunol. 1978; 8(7):477-84. DOI: 10.1002/eji.1830080706. View

14.

Klinkert M, Theilmann L, Pfaff E, Schaller H . Pre-S1 antigens and antibodies early in the course of acute hepatitis B virus infection. J Virol. 1986; 58(2):522-5. PMC: 252940. DOI: 10.1128/JVI.58.2.522-525.1986. View

15.

Gebel H, Scott J, Parvin C, Rodey G . In vitro immunization to KLH. II. Limiting dilution analysis of antigen-reactive cells in primary and secondary culture. J Immunol. 1983; 130(1):29-32. View

16.

McALEER W, BUYNAK E, Maigetter R, WAMPLER D, MILLER W, HILLEMAN M . Human hepatitis B vaccine from recombinant yeast. Nature. 1984; 307(5947):178-80. DOI: 10.1038/307178a0. View

17.

Celis E, Kung P, Chang T . Hepatitis B virus-reactive human T lymphocyte clones: antigen specificity and helper function for antibody synthesis. J Immunol. 1984; 132(3):1511-6. View

18.

Alberti A, Pontisso P, Schiavon E, Realdi G . An antibody which precipitates Dane particles in acute hepatitis type B: relation to receptor sites which bind polymerized human serum albumin on virus particles. Hepatology. 1984; 4(2):220-6. DOI: 10.1002/hep.1840040209. View

19.

Celis E, Chang T . Antibodies to hepatitis B surface antigen potentiate the response of human T lymphocyte clones to the same antigen. Science. 1984; 224(4646):297-9. DOI: 10.1126/science.6231724. View

20.

Milich D, Peterson D, Leroux-Roels G, Lerner R, Chisari F . Genetic regulation of the immune response to hepatitis B surface antigen (HBsAg). VI. T cell fine specificity. J Immunol. 1985; 134(6):4203-11. View