Agadjanyan M, Kim J, Weiner D; International Conference on AIDS.
Int Conf AIDS. 1998; 12: 277 (abstract no. 21195).
University of Pennsylvania, Philadelphia, USA.
DNA plasmid based immunization has emerged recently as a promising novel vaccine strategy and our laboratory has been investigating the potential of this technique for the development of a vaccine against HIV since 1993. Muscle tissue has previously been demonstrated to be a major site of antigen expression after intramuscular injection of DNA vaccines. Unlike professional antigen presenting cells (APCs), however, muscle cells do not express the costimulatory molecules CD80 (B7-1) or CD86 (B7-2) which provide critical secondary signals for T-cell activation. Recently we the first time presented data demonstrating that co-inoculation of mice with DNA plasmids encoding HIV-1 antigens with genes for CD86 dramatically increased antigen-specific T-cell responses without a significant change in humoral immune response. To resolve whether muscle cells or professional APCs are responsible for enhancement of anti-viral CTL following CD86 co-inoculation, we constructed a set of bone marrow chimeric animals using mice bearing a genetic disruption of beta 2-microglobulin (beta 2 m). The relationship between CTL induction and MHC class I-restriction after expression of both viral antigen and CD80 or CD86 costimulatory molecule genes was determined. MHC class I-restriction of CTL was determined to be under the providence of the B7-2 (CD86) molecule, even when this molecule and antigen were displayed on a non-professional antigen presenting cell background. This study defines a role of CD86 in CTL immune induction during DNA immunization. Our results demonstrated that non-hematopoeitic cells, most likely muscle cells, can be engineered to present the viral antigen.
Publication Types:
Keywords:
- AIDS Vaccines
- Animals
- Antigen-Presenting Cells
- Antigens, CD
- Antigens, CD80
- Antigens, Viral
- CD86 protein, human
- Genes, MHC Class I
- Lymphocyte Activation
- Membrane Glycoproteins
- Mice
- Resin Cements
- T-Lymphocytes, Cytotoxic
- Vaccines, DNA
- beta 2-Microglobulin
- genetics
- immunology
Other ID:
UI: 102228734
From Meeting Abstracts