Abstract
Striated muscle is the predominant site of gene expression after i.m. immunization of plasmid DNA, but it is not clear if myocytes or professional antigen-presenting cells (APCs) of hematopoietic origin present the encoded antigens to class I major histocompatibility complex (MHC)-restricted cytotoxic T lymphocytes (CTL). To address this issue, CTL responses were assessed in mice engrafted with immune systems that were partially MHC matched with antigen-producing muscle cells. Spleen cells (sc) from immunocompetent F1 H-2bxd mice were infused into H-2b or H-2d mice carrying the severe combined immunodeficiency (scid) mutation, creating F1sc-->H-2b and F1sc-->H-2d chimeras, respectively. Immunization with DNA plasmids encoding the herpes simplex virus gB or the human immunodeficiency virus gp120 glycoproteins elicited antiviral CTL activity. F1sc-->H-2d chimeras responded to an H-2d-restricted gp120 epitope but not an H-2b restricted gB epitope, whereas F1sc-->H-2b chimeras responded to the H-2b but not the H-2d restricted epitope. This pattern of epitope recognition by the sc chimeras indicated that APCs of recipient (scid) origin were involved in initiation of CTL responses. Significantly, CTL responses against epitopes presented by the mismatched donor class I molecules were elicited if F1 bone marrow cells and sc were transferred into scid recipients before or several days to weeks after DNA immunization. Thus, bone marrow-derived APCs are sufficient for class I MHC presentation of viral antigens after i.m. immunization with plasmid DNA. Expression of plasmid DNA by these APCs is probably not a requirement for CTL priming. Instead, they appear to present proteins synthesized by other host cells.
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Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bevan M. J. Antigen presentation to cytotoxic T lymphocytes in vivo. J Exp Med. 1995 Sep 1;182(3):639–641. doi: 10.1084/jem.182.3.639. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bevan M. J. Antigen recognition. Class discrimination in the world of immunology. Nature. 1987 Jan 15;325(6101):192–194. doi: 10.1038/325192b0. [DOI] [PubMed] [Google Scholar]
- Brodsky F. M., Guagliardi L. E. The cell biology of antigen processing and presentation. Annu Rev Immunol. 1991;9:707–744. doi: 10.1146/annurev.iy.09.040191.003423. [DOI] [PubMed] [Google Scholar]
- Carbone F. R., Bevan M. J. Class I-restricted processing and presentation of exogenous cell-associated antigen in vivo. J Exp Med. 1990 Feb 1;171(2):377–387. doi: 10.1084/jem.171.2.377. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chapman B. S., Thayer R. M., Vincent K. A., Haigwood N. L. Effect of intron A from human cytomegalovirus (Towne) immediate-early gene on heterologous expression in mammalian cells. Nucleic Acids Res. 1991 Jul 25;19(14):3979–3986. doi: 10.1093/nar/19.14.3979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Claesson M. H., Rudolphi A., Tscherning T., Reimann J. CD3+ T cells in severe combined immunodeficiency (scid) mice. IV. Graft-vs.-host resistance of H-2d scid mice to intravenous injection of allogeneic H-2b (C57BL/6) spleen cells. Eur J Immunol. 1991 Sep;21(9):2057–2062. doi: 10.1002/eji.1830210913. [DOI] [PubMed] [Google Scholar]
- Cox G. J., Zamb T. J., Babiuk L. A. Bovine herpesvirus 1: immune responses in mice and cattle injected with plasmid DNA. J Virol. 1993 Sep;67(9):5664–5667. doi: 10.1128/jvi.67.9.5664-5667.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Crowley M. T., Inaba K., Witmer-Pack M. D., Gezelter S., Steinman R. M. Use of the fluorescence activated cell sorter to enrich dendritic cells from mouse spleen. J Immunol Methods. 1990 Oct 4;133(1):55–66. doi: 10.1016/0022-1759(90)90318-p. [DOI] [PubMed] [Google Scholar]
- Czitrom A. A., Edwards S., Phillips R. A., Bosma M. J., Marrack P., Kappler J. W. The function of antigen-presenting cells in mice with severe combined immunodeficiency. J Immunol. 1985 Apr;134(4):2276–2280. [PubMed] [Google Scholar]
- Davis H. L., Whalen R. G., Demeneix B. A. Direct gene transfer into skeletal muscle in vivo: factors affecting efficiency of transfer and stability of expression. Hum Gene Ther. 1993 Apr;4(2):151–159. doi: 10.1089/hum.1993.4.2-151. [DOI] [PubMed] [Google Scholar]
- Debrick J. E., Campbell P. A., Staerz U. D. Macrophages as accessory cells for class I MHC-restricted immune responses. J Immunol. 1991 Nov 1;147(9):2846–2851. [PubMed] [Google Scholar]
- Doe B., Steimer K. S., Walker C. M. Induction of HIV-1 envelope (gp120)-specific cytotoxic T lymphocyte responses in mice by recombinant CHO cell-derived gp120 is enhanced by enzymatic removal of N-linked glycans. Eur J Immunol. 1994 Oct;24(10):2369–2376. doi: 10.1002/eji.1830241017. [DOI] [PubMed] [Google Scholar]
- Doe B., Walker C. M. HIV-1 p24 Gag-specific cytotoxic T-lymphocyte responses in mice. AIDS. 1996 Jun;10(7):793–794. doi: 10.1097/00002030-199606001-00015. [DOI] [PubMed] [Google Scholar]
- Fynan E. F., Webster R. G., Fuller D. H., Haynes J. R., Santoro J. C., Robinson H. L. DNA vaccines: protective immunizations by parenteral, mucosal, and gene-gun inoculations. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11478–11482. doi: 10.1073/pnas.90.24.11478. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goebels N., Michaelis D., Wekerle H., Hohlfeld R. Human myoblasts as antigen-presenting cells. J Immunol. 1992 Jul 15;149(2):661–667. [PubMed] [Google Scholar]
- Haigwood N. L., Nara P. L., Brooks E., Van Nest G. A., Ott G., Higgins K. W., Dunlop N., Scandella C. J., Eichberg J. W., Steimer K. S. Native but not denatured recombinant human immunodeficiency virus type 1 gp120 generates broad-spectrum neutralizing antibodies in baboons. J Virol. 1992 Jan;66(1):172–182. doi: 10.1128/jvi.66.1.172-182.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hanke T., Graham F. L., Rosenthal K. L., Johnson D. C. Identification of an immunodominant cytotoxic T-lymphocyte recognition site in glycoprotein B of herpes simplex virus by using recombinant adenovirus vectors and synthetic peptides. J Virol. 1991 Mar;65(3):1177–1186. doi: 10.1128/jvi.65.3.1177-1186.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harlan D. M., Hengartner H., Huang M. L., Kang Y. H., Abe R., Moreadith R. W., Pircher H., Gray G. S., Ohashi P. S., Freeman G. J. Mice expressing both B7-1 and viral glycoprotein on pancreatic beta cells along with glycoprotein-specific transgenic T cells develop diabetes due to a breakdown of T-lymphocyte unresponsiveness. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3137–3141. doi: 10.1073/pnas.91.8.3137. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hohlfeld R., Engel A. G. The immunobiology of muscle. Immunol Today. 1994 Jun;15(6):269–274. doi: 10.1016/0167-5699(94)90006-X. [DOI] [PubMed] [Google Scholar]
- Huang A. Y., Golumbek P., Ahmadzadeh M., Jaffee E., Pardoll D., Levitsky H. Role of bone marrow-derived cells in presenting MHC class I-restricted tumor antigens. Science. 1994 May 13;264(5161):961–965. doi: 10.1126/science.7513904. [DOI] [PubMed] [Google Scholar]
- Inaba K., Inaba M., Deguchi M., Hagi K., Yasumizu R., Ikehara S., Muramatsu S., Steinman R. M. Granulocytes, macrophages, and dendritic cells arise from a common major histocompatibility complex class II-negative progenitor in mouse bone marrow. Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):3038–3042. doi: 10.1073/pnas.90.7.3038. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Inaba K., Inaba M., Romani N., Aya H., Deguchi M., Ikehara S., Muramatsu S., Steinman R. M. Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. J Exp Med. 1992 Dec 1;176(6):1693–1702. doi: 10.1084/jem.176.6.1693. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jiao S., Williams P., Berg R. K., Hodgeman B. A., Liu L., Repetto G., Wolff J. A. Direct gene transfer into nonhuman primate myofibers in vivo. Hum Gene Ther. 1992 Feb;3(1):21–33. doi: 10.1089/hum.1992.3.1-21. [DOI] [PubMed] [Google Scholar]
- June C. H., Bluestone J. A., Nadler L. M., Thompson C. B. The B7 and CD28 receptor families. Immunol Today. 1994 Jul;15(7):321–331. doi: 10.1016/0167-5699(94)90080-9. [DOI] [PubMed] [Google Scholar]
- Kovacsovics-Bankowski M., Clark K., Benacerraf B., Rock K. L. Efficient major histocompatibility complex class I presentation of exogenous antigen upon phagocytosis by macrophages. Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):4942–4946. doi: 10.1073/pnas.90.11.4942. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kovacsovics-Bankowski M., Rock K. L. A phagosome-to-cytosol pathway for exogenous antigens presented on MHC class I molecules. Science. 1995 Jan 13;267(5195):243–246. doi: 10.1126/science.7809629. [DOI] [PubMed] [Google Scholar]
- Kündig T. M., Bachmann M. F., DiPaolo C., Simard J. J., Battegay M., Lother H., Gessner A., Kühlcke K., Ohashi P. S., Hengartner H. Fibroblasts as efficient antigen-presenting cells in lymphoid organs. Science. 1995 Jun 2;268(5215):1343–1347. doi: 10.1126/science.7761853. [DOI] [PubMed] [Google Scholar]
- Norbury C. C., Hewlett L. J., Prescott A. R., Shastri N., Watts C. Class I MHC presentation of exogenous soluble antigen via macropinocytosis in bone marrow macrophages. Immunity. 1995 Dec;3(6):783–791. doi: 10.1016/1074-7613(95)90067-5. [DOI] [PubMed] [Google Scholar]
- Paglia P., Chiodoni C., Rodolfo M., Colombo M. P. Murine dendritic cells loaded in vitro with soluble protein prime cytotoxic T lymphocytes against tumor antigen in vivo. J Exp Med. 1996 Jan 1;183(1):317–322. doi: 10.1084/jem.183.1.317. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pardoll D. M., Beckerleg A. M. Exposing the immunology of naked DNA vaccines. Immunity. 1995 Aug;3(2):165–169. doi: 10.1016/1074-7613(95)90085-3. [DOI] [PubMed] [Google Scholar]
- Pfeifer J. D., Wick M. J., Roberts R. L., Findlay K., Normark S. J., Harding C. V. Phagocytic processing of bacterial antigens for class I MHC presentation to T cells. Nature. 1993 Jan 28;361(6410):359–362. doi: 10.1038/361359a0. [DOI] [PubMed] [Google Scholar]
- Raz E., Carson D. A., Parker S. E., Parr T. B., Abai A. M., Aichinger G., Gromkowski S. H., Singh M., Lew D., Yankauckas M. A. Intradermal gene immunization: the possible role of DNA uptake in the induction of cellular immunity to viruses. Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9519–9523. doi: 10.1073/pnas.91.20.9519. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rudolphi A., Spiess S., Conradt P., Claesson M. H., Reimann J. CD3+ T cells in severe combined immunodeficiency (scid) mice. II. Transplantation of dm2 lymphoid cells into semi-allogeneic scid mice. Eur J Immunol. 1991 Jul;21(7):1591–1600. doi: 10.1002/eji.1830210704. [DOI] [PubMed] [Google Scholar]
- Scheicher C., Mehlig M., Zecher R., Reske K. Dendritic cells from mouse bone marrow: in vitro differentiation using low doses of recombinant granulocyte-macrophage colony-stimulating factor. J Immunol Methods. 1992 Oct 2;154(2):253–264. doi: 10.1016/0022-1759(92)90199-4. [DOI] [PubMed] [Google Scholar]
- Sedegah M., Hedstrom R., Hobart P., Hoffman S. L. Protection against malaria by immunization with plasmid DNA encoding circumsporozoite protein. Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9866–9870. doi: 10.1073/pnas.91.21.9866. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sunshine G. H., Jimmo B. L., Ianelli C., Jarvis L. Strong priming of T cells adoptively transferred into scid mice. J Exp Med. 1991 Dec 1;174(6):1653–1656. doi: 10.1084/jem.174.6.1653. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Takahashi H., Cohen J., Hosmalin A., Cease K. B., Houghten R., Cornette J. L., DeLisi C., Moss B., Germain R. N., Berzofsky J. A. An immunodominant epitope of the human immunodeficiency virus envelope glycoprotein gp160 recognized by class I major histocompatibility complex molecule-restricted murine cytotoxic T lymphocytes. Proc Natl Acad Sci U S A. 1988 May;85(9):3105–3109. doi: 10.1073/pnas.85.9.3105. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tang D. C., DeVit M., Johnston S. A. Genetic immunization is a simple method for eliciting an immune response. Nature. 1992 Mar 12;356(6365):152–154. doi: 10.1038/356152a0. [DOI] [PubMed] [Google Scholar]
- Ulmer J. B., Donnelly J. J., Parker S. E., Rhodes G. H., Felgner P. L., Dwarki V. J., Gromkowski S. H., Deck R. R., DeWitt C. M., Friedman A. Heterologous protection against influenza by injection of DNA encoding a viral protein. Science. 1993 Mar 19;259(5102):1745–1749. doi: 10.1126/science.8456302. [DOI] [PubMed] [Google Scholar]
- Wang B., Ugen K. E., Srikantan V., Agadjanyan M. G., Dang K., Refaeli Y., Sato A. I., Boyer J., Williams W. V., Weiner D. B. Gene inoculation generates immune responses against human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1993 May 1;90(9):4156–4160. doi: 10.1073/pnas.90.9.4156. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wolff J. A., Malone R. W., Williams P., Chong W., Acsadi G., Jani A., Felgner P. L. Direct gene transfer into mouse muscle in vivo. Science. 1990 Mar 23;247(4949 Pt 1):1465–1468. doi: 10.1126/science.1690918. [DOI] [PubMed] [Google Scholar]
- Zinkernagel R. M., Rüedi E., Althage A., Hengartner H., Reimann G. Thymic selection of H-2-incompatible bone marrow cells in SCID mice. Differences in T help for induction of B cell IgG responses versus cytotoxic T cells. J Exp Med. 1988 Sep 1;168(3):1187–1192. doi: 10.1084/jem.168.3.1187. [DOI] [PMC free article] [PubMed] [Google Scholar]