Truncated or chimeric endogenous protein antigens gain immunogenicity for B cells by stress protein‐facilitated expression

• Published in: European journal of immunology 1999-05, Vol.29 (5), p.1740-1749
• Main Authors: Schirmbeck, Reinhold, Gerstner, Ortrud, Reimann, Jörg
• Format: Article
• Language: English
• Subjects: Animals; Antibody response; Antigens, Polyomavirus Transforming - genetics; Antigens, Polyomavirus Transforming - immunology; B-Lymphocytes - immunology; Carrier Proteins - genetics; Carrier Proteins - immunology; DNA vaccination; Gene Expression Regulation; Hepatitis B Antibodies - immunology; Hepatitis B Surface Antigens - genetics; Hepatitis B Surface Antigens - immunology; HSC70 Heat-Shock Proteins; HSP70 Heat-Shock Proteins; Humans; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Plasmids; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - immunology; Stress protein; Vaccination
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/(SICI)1521-4141(199905)29:05<1740::AID-IMMU1740>3.0.CO;2-X

Truncated variants of the SV40 large T antigen (T‐Ag) with an intact N terminus are as efficiently expressed in eukaryotic transfectants as wild‐type (wt) T‐Ag. Coprecipitation of N‐terminal T‐Ag fragments with the constitutively expressed, cytosolic stress protein hsp73 suggests that this chaperone stabilized expression of the truncated T‐Ag fragments. In contrast to T‐Ag, the 163‐residue N‐terminal preS domain of the hepatitis B surface antigen (HBsAg) is difficult to express. When the preS domain is C‐terminally fused to a hsp73‐binding cytoplasmic T‐Ag (cT‐Ag) fragment its stable expression as a chimeric cT‐preS protein is obtained. DNA‐based vaccination with plasmid DNA encoding either wt or hsp‐associated mutant T‐Ag elicited potent MHC class I‐restricted, T‐Ag‐specific T cell responses. In contrast, DNA vaccination with hsp73‐binding (mutant or chimeric) T‐Ag variants, but not with wt T‐Ag elicited T‐Ag‐specific antibody responses. Furthermore, vaccination with cT‐preS‐encoding plasmid DNA induced antibodies binding to the preS domain of the large HBsAg. Hence, hsp73‐bound endogenous antigens efficiently stimulate antibody responses. These findings may be relevant for tumor immunology and autoimmunity.