Abstract
The neisserial porins are the major protein components of the outer membrane of the pathogenic Neisseria (N. meningitidis and N. gonorrhoeae). They have been shown to be able to enhance the immune response to poorly immunogenic substances (e.g., polysaccharides, peptides, glycolipids, etc.). To explore the basis of their potent adjuvant activity, the effect of the neisserial porins on T-B cell interactions and T cell costimulation was examined. Neisserial porins increased the surface expression of the costimulatory ligand B7-2 (CD86) but did not affect the expression of B7-1 (CD80). In addition, incubation with the neisserial porins increased the T lymphocyte costimulatory ability of B lymphocytes, which was inhibited by anti-B7- 2 but not anti-B7-1 monoclonal antibodies. Upregulation of B7-2 on the surface of B lymphocytes may be the mechanism behind the immunopotentiating activity of neisserial porins.
Full Text
The Full Text of this article is available as a PDF (1.2 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bjune G., Høiby E. A., Grønnesby J. K., Arnesen O., Fredriksen J. H., Halstensen A., Holten E., Lindbak A. K., Nøkleby H., Rosenqvist E. Effect of outer membrane vesicle vaccine against group B meningococcal disease in Norway. Lancet. 1991 Nov 2;338(8775):1093–1096. doi: 10.1016/0140-6736(91)91961-s. [DOI] [PubMed] [Google Scholar]
- Blake M. S., Gotschlich E. C. Purification and partial characterization of the major outer membrane protein of Neisseria gonorrhoeae. Infect Immun. 1982 Apr;36(1):277–283. doi: 10.1128/iai.36.1.277-283.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Blake M. S., Gotschlich E. C. Purification and partial characterization of the opacity-associated proteins of Neisseria gonorrhoeae. J Exp Med. 1984 Feb 1;159(2):452–462. doi: 10.1084/jem.159.2.452. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Blazar B. R., Taylor P. A., Linsley P. S., Vallera D. A. In vivo blockade of CD28/CTLA4: B7/BB1 interaction with CTLA4-Ig reduces lethal murine graft-versus-host disease across the major histocompatibility complex barrier in mice. Blood. 1994 Jun 15;83(12):3815–3825. [PubMed] [Google Scholar]
- Butcher S., Sarvas M., Runeberg-Nyman K. Class-3 porin protein of Neisseria meningitidis: cloning and structure of the gene. Gene. 1991 Aug 30;105(1):125–128. doi: 10.1016/0378-1119(91)90523-e. [DOI] [PubMed] [Google Scholar]
- Carbonetti N. H., Sparling P. F. Molecular cloning and characterization of the structural gene for protein I, the major outer membrane protein of Neisseria gonorrhoeae. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9084–9088. doi: 10.1073/pnas.84.24.9084. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Caux C., Massacrier C., Vanbervliet B., Dubois B., Van Kooten C., Durand I., Banchereau J. Activation of human dendritic cells through CD40 cross-linking. J Exp Med. 1994 Oct 1;180(4):1263–1272. doi: 10.1084/jem.180.4.1263. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Damle N. K., Linsley P. S., Ledbetter J. A. Direct helper T cell-induced B cell differentiation involves interaction between T cell antigen CD28 and B cell activation antigen B7. Eur J Immunol. 1991 May;21(5):1277–1282. doi: 10.1002/eji.1830210527. [DOI] [PubMed] [Google Scholar]
- Donnelly J. J., Deck R. R., Liu M. A. Immunogenicity of a Haemophilus influenzae polysaccharide-Neisseria meningitidis outer membrane protein complex conjugate vaccine. J Immunol. 1990 Nov 1;145(9):3071–3079. [PubMed] [Google Scholar]
- Engel P., Gribben J. G., Freeman G. J., Zhou L. J., Nozawa Y., Abe M., Nadler L. M., Wakasa H., Tedder T. F. The B7-2 (B70) costimulatory molecule expressed by monocytes and activated B lymphocytes is the CD86 differentiation antigen. Blood. 1994 Sep 1;84(5):1402–1407. [PubMed] [Google Scholar]
- Freeman G. J., Borriello F., Hodes R. J., Reiser H., Gribben J. G., Ng J. W., Kim J., Goldberg J. M., Hathcock K., Laszlo G. Murine B7-2, an alternative CTLA4 counter-receptor that costimulates T cell proliferation and interleukin 2 production. J Exp Med. 1993 Dec 1;178(6):2185–2192. doi: 10.1084/jem.178.6.2185. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Freeman G. J., Borriello F., Hodes R. J., Reiser H., Hathcock K. S., Laszlo G., McKnight A. J., Kim J., Du L., Lombard D. B. Uncovering of functional alternative CTLA-4 counter-receptor in B7-deficient mice. Science. 1993 Nov 5;262(5135):907–909. doi: 10.1126/science.7694362. [DOI] [PubMed] [Google Scholar]
- Freeman G. J., Freedman A. S., Segil J. M., Lee G., Whitman J. F., Nadler L. M. B7, a new member of the Ig superfamily with unique expression on activated and neoplastic B cells. J Immunol. 1989 Oct 15;143(8):2714–2722. [PubMed] [Google Scholar]
- Freeman G. J., Gribben J. G., Boussiotis V. A., Ng J. W., Restivo V. A., Jr, Lombard L. A., Gray G. S., Nadler L. M. Cloning of B7-2: a CTLA-4 counter-receptor that costimulates human T cell proliferation. Science. 1993 Nov 5;262(5135):909–911. doi: 10.1126/science.7694363. [DOI] [PubMed] [Google Scholar]
- Gotschlich E. C., Seiff M. E., Blake M. S., Koomey M. Porin protein of Neisseria gonorrhoeae: cloning and gene structure. Proc Natl Acad Sci U S A. 1987 Nov;84(22):8135–8139. doi: 10.1073/pnas.84.22.8135. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Guttormsen H. K., Wetzler L. M., Naess A. Humoral immune response to the class 3 outer membrane protein during the course of meningococcal disease. Infect Immun. 1993 Nov;61(11):4734–4742. doi: 10.1128/iai.61.11.4734-4742.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Guttormsen H. K., Wetzler L. M., Solberg C. O. Humoral immune response to class 1 outer membrane protein during the course of meningococcal disease. Infect Immun. 1994 Apr;62(4):1437–1443. doi: 10.1128/iai.62.4.1437-1443.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hathcock K. S., Laszlo G., Dickler H. B., Bradshaw J., Linsley P., Hodes R. J. Identification of an alternative CTLA-4 ligand costimulatory for T cell activation. Science. 1993 Nov 5;262(5135):905–907. doi: 10.1126/science.7694361. [DOI] [PubMed] [Google Scholar]
- Hathcock K. S., Laszlo G., Pucillo C., Linsley P., Hodes R. J. Comparative analysis of B7-1 and B7-2 costimulatory ligands: expression and function. J Exp Med. 1994 Aug 1;180(2):631–640. doi: 10.1084/jem.180.2.631. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Inaba K., Witmer-Pack M., Inaba M., Hathcock K. S., Sakuta H., Azuma M., Yagita H., Okumura K., Linsley P. S., Ikehara S. The tissue distribution of the B7-2 costimulator in mice: abundant expression on dendritic cells in situ and during maturation in vitro. J Exp Med. 1994 Nov 1;180(5):1849–1860. doi: 10.1084/jem.180.5.1849. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Janeway C. A., Jr, Bottomly K. Signals and signs for lymphocyte responses. Cell. 1994 Jan 28;76(2):275–285. doi: 10.1016/0092-8674(94)90335-2. [DOI] [PubMed] [Google Scholar]
- Janeway C. Immunogenicity signals 1,2,3 ... and 0. Immunol Today. 1989 Sep;10(9):283–286. doi: 10.1016/0167-5699(89)90081-9. [DOI] [PubMed] [Google Scholar]
- Jeanteur D., Lakey J. H., Pattus F. The bacterial porin superfamily: sequence alignment and structure prediction. Mol Microbiol. 1991 Sep;5(9):2153–2164. doi: 10.1111/j.1365-2958.1991.tb02145.x. [DOI] [PubMed] [Google Scholar]
- Jenkins M. K. The ups and downs of T cell costimulation. Immunity. 1994 Sep;1(6):443–446. doi: 10.1016/1074-7613(94)90086-8. [DOI] [PubMed] [Google Scholar]
- Klugman K. P., Gotschlich E. C., Blake M. S. Sequence of the structural gene (rmpM) for the class 4 outer membrane protein of Neisseria meningitidis, homology of the protein to gonococcal protein III and Escherichia coli OmpA, and construction of meningococcal strains that lack class 4 protein. Infect Immun. 1989 Jul;57(7):2066–2071. doi: 10.1128/iai.57.7.2066-2071.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kwekkeboom J., de Rijk D., Kasran A., Barcy S., de Groot C., de Boer M. Helper effector function of human T cells stimulated by anti-CD3 mAb can be enhanced by co-stimulatory signals and is partially dependent on CD40-CD40 ligand interaction. Eur J Immunol. 1994 Mar;24(3):508–517. doi: 10.1002/eji.1830240303. [DOI] [PubMed] [Google Scholar]
- Larsen C. P., Ritchie S. C., Hendrix R., Linsley P. S., Hathcock K. S., Hodes R. J., Lowry R. P., Pearson T. C. Regulation of immunostimulatory function and costimulatory molecule (B7-1 and B7-2) expression on murine dendritic cells. J Immunol. 1994 Jun 1;152(11):5208–5219. [PubMed] [Google Scholar]
- Lenschow D. J., Sperling A. I., Cooke M. P., Freeman G., Rhee L., Decker D. C., Gray G., Nadler L. M., Goodnow C. C., Bluestone J. A. Differential up-regulation of the B7-1 and B7-2 costimulatory molecules after Ig receptor engagement by antigen. J Immunol. 1994 Sep 1;153(5):1990–1997. [PubMed] [Google Scholar]
- Liu Y., Janeway C. A., Jr Microbial induction of co-stimulatory activity for CD4 T-cell growth. Int Immunol. 1991 Apr;3(4):323–332. doi: 10.1093/intimm/3.4.323. [DOI] [PubMed] [Google Scholar]
- Liu Y., Jones B., Brady W., Janeway C. A., Jr, Linsley P. S., Linley P. S. Co-stimulation of murine CD4 T cell growth: cooperation between B7 and heat-stable antigen. Eur J Immunol. 1992 Nov;22(11):2855–2859. doi: 10.1002/eji.1830221115. [DOI] [PubMed] [Google Scholar]
- Liu Y., Linsley P. S. Costimulation of T-cell growth. Curr Opin Immunol. 1992 Jun;4(3):265–270. doi: 10.1016/0952-7915(92)90075-p. [DOI] [PubMed] [Google Scholar]
- Livingston P. O., Calves M. J., Helling F., Zollinger W. D., Blake M. S., Lowell G. H. GD3/proteosome vaccines induce consistent IgM antibodies against the ganglioside GD3. Vaccine. 1993 Sep;11(12):1199–1204. doi: 10.1016/0264-410x(93)90043-w. [DOI] [PubMed] [Google Scholar]
- Lowell G. H., Ballou W. R., Smith L. F., Wirtz R. A., Zollinger W. D., Hockmeyer W. T. Proteosome-lipopeptide vaccines: enhancement of immunogenicity for malaria CS peptides. Science. 1988 May 6;240(4853):800–802. doi: 10.1126/science.2452484. [DOI] [PubMed] [Google Scholar]
- Mauro A., Blake M., Labarca P. Voltage gating of conductance in lipid bilayers induced by porin from outer membrane of Neisseria gonorrhoeae. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1071–1075. doi: 10.1073/pnas.85.4.1071. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Melancon J., Murgita R. A., Devoe I. W. Activation of murine B lymphocytes by Neisseria meningitidis and isolated meningococcal surface antigens. Infect Immun. 1983 Nov;42(2):471–479. doi: 10.1128/iai.42.2.471-479.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Murakami K., Gotschlich E. C., Seiff M. E. Cloning and characterization of the structural gene for the class 2 protein of Neisseria meningitidis. Infect Immun. 1989 Aug;57(8):2318–2323. doi: 10.1128/iai.57.8.2318-2323.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Noelle R. J., Snow E. C. T helper cell-dependent B cell activation. FASEB J. 1991 Oct;5(13):2770–2776. doi: 10.1096/fasebj.5.13.1833257. [DOI] [PubMed] [Google Scholar]
- Paul W. E., Seder R. A. Lymphocyte responses and cytokines. Cell. 1994 Jan 28;76(2):241–251. doi: 10.1016/0092-8674(94)90332-8. [DOI] [PubMed] [Google Scholar]
- Poolman J. T. Meningococcal vaccines. J Med Microbiol. 1988 Jul;26(3):170–172. [PubMed] [Google Scholar]
- Razi-Wolf Z., Freeman G. J., Galvin F., Benacerraf B., Nadler L., Reiser H. Expression and function of the murine B7 antigen, the major costimulatory molecule expressed by peritoneal exudate cells. Proc Natl Acad Sci U S A. 1992 May 1;89(9):4210–4214. doi: 10.1073/pnas.89.9.4210. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Razi-Wolf Z., Galvin F., Gray G., Reiser H. Evidence for an additional ligand, distinct from B7, for the CTLA-4 receptor. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11182–11186. doi: 10.1073/pnas.90.23.11182. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reiser H., Benacerraf B. Costimulatory signal provided by a B-lymphoblastoid cell line and its Ia-negative variant. Proc Natl Acad Sci U S A. 1989 Dec;86(24):10069–10073. doi: 10.1073/pnas.86.24.10069. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reiser H., Freeman G. J., Razi-Wolf Z., Gimmi C. D., Benacerraf B., Nadler L. M. Murine B7 antigen provides an efficient costimulatory signal for activation of murine T lymphocytes via the T-cell receptor/CD3 complex. Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):271–275. doi: 10.1073/pnas.89.1.271. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schwartz R. H. Costimulation of T lymphocytes: the role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy. Cell. 1992 Dec 24;71(7):1065–1068. doi: 10.1016/s0092-8674(05)80055-8. [DOI] [PubMed] [Google Scholar]
- Sparkes B. G. Dual effect of meningococcal antigens on a T cell dependent immune response. Can J Microbiol. 1983 Dec;29(12):1619–1625. doi: 10.1139/m83-248. [DOI] [PubMed] [Google Scholar]
- Sparkes B. G. Immunomodulating activity of meningococcal antigens. Can J Microbiol. 1983 Dec;29(12):1611–1618. doi: 10.1139/m83-247. [DOI] [PubMed] [Google Scholar]
- Sultzer B. M., Castagna R., Bandekar J., Wong P. Lipopolysaccharide nonresponder cells: the C3H/HeJ defect. Immunobiology. 1993 Apr;187(3-5):257–271. doi: 10.1016/S0171-2985(11)80343-8. [DOI] [PubMed] [Google Scholar]
- Vandenberghe P., Delabie J., de Boer M., De Wolf-Peeters C., Ceuppens J. L. In situ expression of B7/BB1 on antigen-presenting cells and activated B cells: an immunohistochemical study. Int Immunol. 1993 Mar;5(3):317–321. doi: 10.1093/intimm/5.3.317. [DOI] [PubMed] [Google Scholar]
- Vetvicka V., Lee G., Kincade P. W. Intrinsic B lymphocyte and macrophage defects in C3H/HeJ mice. J Immunol. 1986 Apr 1;136(7):2370–2374. [PubMed] [Google Scholar]
- Vordermeier H. M., Bessler W. G. Polyclonal activation of murine B lymphocytes in vitro by Salmonella typhimurium porins. Immunobiology. 1987 Sep;175(3):245–251. doi: 10.1016/S0171-2985(87)80033-5. [DOI] [PubMed] [Google Scholar]
- Vordermeier H. M., Drexler H., Bessler W. G. Polyclonal activation of human peripheral blood lymphocytes by bacterial porins and defined porin fragments. Immunol Lett. 1987 Jun;15(2):121–126. doi: 10.1016/0165-2478(87)90042-3. [DOI] [PubMed] [Google Scholar]
- Ward M. J., Lambden P. R., Heckels J. E. Sequence analysis and relationships between meningococcal class 3 serotype proteins and other porins from pathogenic and non-pathogenic Neisseria species. FEMS Microbiol Lett. 1992 Jul 15;73(3):283–289. doi: 10.1016/0378-1097(92)90644-4. [DOI] [PubMed] [Google Scholar]
- Wetzler L. M., Blake M. S., Barry K., Gotschlich E. C. Gonococcal porin vaccine evaluation: comparison of Por proteosomes, liposomes, and blebs isolated from rmp deletion mutants. J Infect Dis. 1992 Sep;166(3):551–555. doi: 10.1093/infdis/166.3.551. [DOI] [PubMed] [Google Scholar]
- Wetzler L. M., Blake M. S., Gotschlich E. C. Characterization and specificity of antibodies to protein I of Neisseria gonorrhoeae produced by injection with various protein I-adjuvant preparations. J Exp Med. 1988 Nov 1;168(5):1883–1897. doi: 10.1084/jem.168.5.1883. [DOI] [PMC free article] [PubMed] [Google Scholar]