Abstract
To investigate the antigenic variation and relationships of immunoglobulin A1 (IgA1) proteases among different species and genera, we examined a comprehensive collection of serine type and metallo-type IgA1 proteases and corresponding antisera in enzyme neutralization assays. Sharing of neutralizing epitopes of metallo-type IgA1 proteases from Streptococcus pneumoniae, Streptococcus sanguis, Streptococcus mitis, and Streptococcus oralis and of serine type IgA1 proteases from Haemophilus and pathogenic Neisseria species was extremely limited. A number of limited to strong cross-reactions in such epitopes were found among serine type IgA1 proteases released by members of the genera Haemophilus and Neisseria, reflecting the common origin of their iga gene. However, the relatively limited prevalence of shared "neutralizing" epitopes of IgA1 proteases from the two genera indicates that they rarely induce immunity to each other. In contrast, extensive sharing of neutralizing epitopes was found between N. meningitidis and N. gonorrhoeae IgA1 proteases, making them potentially attractive vaccine components. Among metallo-type IgA1 proteases, several pneumococcal proteases were found to induce neutralizing antibodies to IgA1 proteases of oral streptococci whereas the opposite was not the case.
Full text
PDF





Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ahl T., Reinholdt J. Detection of immunoglobulin A1 protease-induced Fab alpha fragments on dental plaque bacteria. Infect Immun. 1991 Feb;59(2):563–569. doi: 10.1128/iai.59.2.563-569.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bachovchin W. W., Plaut A. G., Flentke G. R., Lynch M., Kettner C. A. Inhibition of IgA1 proteinases from Neisseria gonorrhoeae and Hemophilus influenzae by peptide prolyl boronic acids. J Biol Chem. 1990 Mar 5;265(7):3738–3743. [PubMed] [Google Scholar]
- Brooks G. F., Lammel C. J., Blake M. S., Kusecek B., Achtman M. Antibodies against IgA1 protease are stimulated both by clinical disease and asymptomatic carriage of serogroup A Neisseria meningitidis. J Infect Dis. 1992 Dec;166(6):1316–1321. doi: 10.1093/infdis/166.6.1316. [DOI] [PubMed] [Google Scholar]
- Caugant D. A., Kristiansen B. E., Frøholm L. O., Bøvre K., Selander R. K. Clonal diversity of Neisseria meningitidis from a population of asymptomatic carriers. Infect Immun. 1988 Aug;56(8):2060–2068. doi: 10.1128/iai.56.8.2060-2068.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Devenyi A. G., Plaut A. G., Grundy F. J., Wright A. Post-infectious human serum antibodies inhibit IgA1 proteinases by interaction with the cleavage site specificity determinant. Mol Immunol. 1993 Oct;30(14):1243–1248. doi: 10.1016/0161-5890(93)90039-e. [DOI] [PubMed] [Google Scholar]
- Gilbert J. V., Plaut A. G., Fishman Y., Wright A. Cloning of the gene encoding streptococcal immunoglobulin A protease and its expression in Escherichia coli. Infect Immun. 1988 Aug;56(8):1961–1966. doi: 10.1128/iai.56.8.1961-1966.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gilbert J. V., Plaut A. G., Longmaid B., Lamm M. E. Inhibition of microbial IgA proteases by human secretory IgA and serum. Mol Immunol. 1983 Sep;20(9):1039–1049. doi: 10.1016/0161-5890(83)90045-7. [DOI] [PubMed] [Google Scholar]
- Gilbert J. V., Plaut A. G., Wright A. Analysis of the immunoglobulin A protease gene of Streptococcus sanguis. Infect Immun. 1991 Jan;59(1):7–17. doi: 10.1128/iai.59.1.7-17.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grundy F. J., Plaut A. G., Wright A. Localization of the cleavage site specificity determinant of Haemophilus influenzae immunoglobulin A1 protease genes. Infect Immun. 1990 Feb;58(2):320–331. doi: 10.1128/iai.58.2.320-331.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Halter R., Pohlner J., Meyer T. F. Mosaic-like organization of IgA protease genes in Neisseria gonorrhoeae generated by horizontal genetic exchange in vivo. EMBO J. 1989 Sep;8(9):2737–2744. doi: 10.1002/j.1460-2075.1989.tb08415.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Higerd T. B., Virella G., Cardenas R., Koistinen J., Fett J. W. New method for obtaining IgA-specific protease. J Immunol Methods. 1977;18(3-4):245–249. doi: 10.1016/0022-1759(77)90178-8. [DOI] [PubMed] [Google Scholar]
- Kett K., Brandtzaeg P., Radl J., Haaijman J. J. Different subclass distribution of IgA-producing cells in human lymphoid organs and various secretory tissues. J Immunol. 1986 May 15;136(10):3631–3635. [PubMed] [Google Scholar]
- Kilian M., Mestecky J., Russell M. W. Defense mechanisms involving Fc-dependent functions of immunoglobulin A and their subversion by bacterial immunoglobulin A proteases. Microbiol Rev. 1988 Jun;52(2):296–303. doi: 10.1128/mr.52.2.296-303.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kilian M., Thomsen B., Petersen T. E., Bleeg H. S. Occurrence and nature of bacterial IgA proteases. Ann N Y Acad Sci. 1983 Jun 30;409:612–624. doi: 10.1111/j.1749-6632.1983.tb26903.x. [DOI] [PubMed] [Google Scholar]
- Kilian M., Thomsen B., Petersen T. E., Bleeg H. Molecular biology of Haemophilus influenzae IgA1 proteases. Mol Immunol. 1983 Sep;20(9):1051–1058. doi: 10.1016/0161-5890(83)90046-9. [DOI] [PubMed] [Google Scholar]
- Kobayashi K., Fujiyama Y., Hagiwara K., Kondoh H. Resistance of normal serum IgA and secretory IgA to bacterial IgA proteases: evidence for the presence of enzyme-neutralizing antibodies in both serum and secretory IgA, and also in serum IgG. Microbiol Immunol. 1987;31(11):1097–1106. doi: 10.1111/j.1348-0421.1987.tb01341.x. [DOI] [PubMed] [Google Scholar]
- Koomey J. M., Falkow S. Nucleotide sequence homology between the immunoglobulin A1 protease genes of Neisseria gonorrhoeae, Neisseria meningitidis, and Haemophilus influenzae. Infect Immun. 1984 Jan;43(1):101–107. doi: 10.1128/iai.43.1.101-107.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kuklinska D., Kilian M. Relative proportions of Haemophilus species in the throat of healthy children and adults. Eur J Clin Microbiol. 1984 Jun;3(3):249–252. doi: 10.1007/BF02014895. [DOI] [PubMed] [Google Scholar]
- Lomholt H., Poulsen K., Caugant D. A., Kilian M. Molecular polymorphism and epidemiology of Neisseria meningitidis immunoglobulin A1 proteases. Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2120–2124. doi: 10.1073/pnas.89.6.2120. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lomholt H., van Alphen L., Kilian M. Antigenic variation of immunoglobulin A1 proteases among sequential isolates of Haemophilus influenzae from healthy children and patients with chronic obstructive pulmonary disease. Infect Immun. 1993 Nov;61(11):4575–4581. doi: 10.1128/iai.61.11.4575-4581.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mansa B., Kilian M. Retained antigen-binding activity of Fab alpha fragments of human monoclonal immunoglobulin A1 (IgA1) cleaved by IgA1 protease. Infect Immun. 1986 Apr;52(1):171–174. doi: 10.1128/iai.52.1.171-174.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Martínez-Maza O., Fehniger T. E., Ashman R. F. Antibody-secreting cell precursor frequencies among the sheep-erythrocyte-binding cells after immunization. Scand J Immunol. 1983 Apr;17(4):345–354. doi: 10.1111/j.1365-3083.1983.tb00799.x. [DOI] [PubMed] [Google Scholar]
- Mestecky J., Kilian M. Immunoglobulin A (IgA). Methods Enzymol. 1985;116:37–75. doi: 10.1016/s0076-6879(85)16005-2. [DOI] [PubMed] [Google Scholar]
- Meyer T. F., Gibbs C. P., Haas R. Variation and control of protein expression in Neisseria. Annu Rev Microbiol. 1990;44:451–477. doi: 10.1146/annurev.mi.44.100190.002315. [DOI] [PubMed] [Google Scholar]
- Mortensen S. B., Kilian M. Purification and characterization of an immunoglobulin A1 protease from Bacteroides melaninogenicus. Infect Immun. 1984 Sep;45(3):550–557. doi: 10.1128/iai.45.3.550-557.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mulks M. H., Simpson D. A., Shoberg R. J. Restriction site polymorphism in genes encoding type 2 but not type 1 gonococcal IgA1 proteases. Antonie Van Leeuwenhoek. 1987;53(6):471–478. doi: 10.1007/BF00415505. [DOI] [PubMed] [Google Scholar]
- Musser J. M., Granoff D. M., Pattison P. E., Selander R. K. A population genetic framework for the study of invasive diseases caused by serotype b strains of Haemophilus influenzae. Proc Natl Acad Sci U S A. 1985 Aug;82(15):5078–5082. doi: 10.1073/pnas.82.15.5078. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Plaut A. G. The IgA1 proteases of pathogenic bacteria. Annu Rev Microbiol. 1983;37:603–622. doi: 10.1146/annurev.mi.37.100183.003131. [DOI] [PubMed] [Google Scholar]
- Pohlner J., Halter R., Beyreuther K., Meyer T. F. Gene structure and extracellular secretion of Neisseria gonorrhoeae IgA protease. 1987 Jan 29-Feb 4Nature. 325(6103):458–462. doi: 10.1038/325458a0. [DOI] [PubMed] [Google Scholar]
- Poulsen K., Hjorth J. P., Kilian M. Limited diversity of the immunoglobulin A1 protease gene (iga) among Haemophilus influenzae serotype b strains. Infect Immun. 1988 Apr;56(4):987–992. doi: 10.1128/iai.56.4.987-992.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Poulsen K., Reinholdt J., Kilian M. A comparative genetic study of serologically distinct Haemophilus influenzae type 1 immunoglobulin A1 proteases. J Bacteriol. 1992 May;174(9):2913–2921. doi: 10.1128/jb.174.9.2913-2921.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reinholdt J., Tomana M., Mortensen S. B., Kilian M. Molecular aspects of immunoglobulin A1 degradation by oral streptococci. Infect Immun. 1990 May;58(5):1186–1194. doi: 10.1128/iai.58.5.1186-1194.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Spinola S. M., Peacock J., Denny F. W., Smith D. L., Cannon J. G. Epidemiology of colonization by nontypable Haemophilus influenzae in children: a longitudinal study. J Infect Dis. 1986 Jul;154(1):100–109. doi: 10.1093/infdis/154.1.100. [DOI] [PubMed] [Google Scholar]
- Trottier S., Stenberg K., Svanborg-Edén C. Turnover of nontypable Haemophilus influenzae in the nasopharynges of healthy children. J Clin Microbiol. 1989 Oct;27(10):2175–2179. doi: 10.1128/jcm.27.10.2175-2179.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]