The cellular interactions responsible for developing the humoral immune response to intracellularly expressed DNA vaccine constructs have not been well characterized. We used a novel mammalian ubiquitin promoter-containing DNA plasmid construct, pTEJ-8, to express mycobacterial heat shock protein 65 (hsp65). To identify specific cell populations involved in the development of the anti-hsp65 humoral immune response, we vaccinated a series of C57BL/6 knock out mice. Using specific anti-hsp65 antibody isotypes as an indication of the in vivo cellular interactions, we observed that wildtype C57BL/6 and γ/δ TcR-/- have similar anti-hsp isotype antibody production that is predominantly IgG2b. CD8-/-, TAP-/- and β2-/- have significantly decreased IgG3 production as compared with wildtype C57BL/6 mice. Mice deficient in α/β TcR-bearing T cells have an almost undetectable anti-hsp65 response which is predominantly IgM and a small amount of IgG3. Interestingly, MHC Class II-/- mice have a weak anti-hsp65 response that contains IgG2b, IgG3, as well as IgM. In vitro studies have shown that isotype class switching results from exposure to specific cytokines. Our results suggest that the T cell type which provides the cytokine help for the humoral response in pTEJ-8/hsp65 vaccinated mice is an α/β TcR-bearing cell and that both the CD4+, and surprisingly, CD8+ T cell compartments play a role in the determination of the anti-hsp65 antibody response.
|Original language||English (US)|
|State||Published - Mar 20 1998|
ASJC Scopus subject areas
- Molecular Biology