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The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1992 Jun 1;175(6):1417–1422. doi: 10.1084/jem.175.6.1417

Serum angiotensin-1 converting enzyme activity processes a human immunodeficiency virus 1 gp160 peptide for presentation by major histocompatibility complex class I molecules

PMCID: PMC2119225  PMID: 1316930

Abstract

T cell stimulation by the human immunodeficiency virus 1 gp160-derived peptide p18 presented by H-2Dd class I major histocompatibility complex molecules in a cell-free system was found to require proteolytic cleavage. This extracellular processing was mediated by peptidases present in fetal calf serum. In vitro processing of p18 resulted in a distinct reverse phase high performance liquid chromatography profile, from which a biologically active product was isolated and sequenced. This peptide processing can be specifically blocked by the angiotensin- 1 converting enzyme (ACE) inhibitor captopril, and can occur by exposing p18 to purified ACE. The ability of naturally occurring extracellular proteases to convert inactive peptides to T cell antigens has important implications for understanding cytotoxic T lymphocyte responses in vivo, and for rational peptide vaccine design.

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Selected References

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  1. Ashwell J. D., Cunningham R. E., Noguchi P. D., Hernandez D. Cell growth cycle block of T cell hybridomas upon activation with antigen. J Exp Med. 1987 Jan 1;165(1):173–194. doi: 10.1084/jem.165.1.173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barrett A. J., Kembhavi A. A., Brown M. A., Kirschke H., Knight C. G., Tamai M., Hanada K. L-trans-Epoxysuccinyl-leucylamido(4-guanidino)butane (E-64) and its analogues as inhibitors of cysteine proteinases including cathepsins B, H and L. Biochem J. 1982 Jan 1;201(1):189–198. doi: 10.1042/bj2010189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Braciale T. J., Morrison L. A., Sweetser M. T., Sambrook J., Gething M. J., Braciale V. L. Antigen presentation pathways to class I and class II MHC-restricted T lymphocytes. Immunol Rev. 1987 Aug;98:95–114. doi: 10.1111/j.1600-065x.1987.tb00521.x. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Clerici M., Lucey D. R., Zajac R. A., Boswell R. N., Gebel H. M., Takahashi H., Berzofsky J. A., Shearer G. M. Detection of cytotoxic T lymphocytes specific for synthetic peptides of gp160 in HIV-seropositive individuals. J Immunol. 1991 Apr 1;146(7):2214–2219. [PubMed] [Google Scholar]
  6. Cushman D. W., Cheung H. S., Sabo E. F., Ondetti M. A. Design of potent competitive inhibitors of angiotensin-converting enzyme. Carboxyalkanoyl and mercaptoalkanoyl amino acids. Biochemistry. 1977 Dec 13;16(25):5484–5491. doi: 10.1021/bi00644a014. [DOI] [PubMed] [Google Scholar]
  7. Diment S., Martin K. J., Stahl P. D. Cleavage of parathyroid hormone in macrophage endosomes illustrates a novel pathway for intracellular processing of proteins. J Biol Chem. 1989 Aug 15;264(23):13403–13406. [PubMed] [Google Scholar]
  8. Falk K., Rötzschke O., Rammensee H. G. Cellular peptide composition governed by major histocompatibility complex class I molecules. Nature. 1990 Nov 15;348(6298):248–251. doi: 10.1038/348248a0. [DOI] [PubMed] [Google Scholar]
  9. Germain R. N. Immunology. The ins and outs of antigen processing and presentation. Nature. 1986 Aug 21;322(6081):687–689. doi: 10.1038/322687a0. [DOI] [PubMed] [Google Scholar]
  10. Jardetzky T. S., Lane W. S., Robinson R. A., Madden D. R., Wiley D. C. Identification of self peptides bound to purified HLA-B27. Nature. 1991 Sep 26;353(6342):326–329. doi: 10.1038/353326a0. [DOI] [PubMed] [Google Scholar]
  11. Kane K. P., Sherman L. A., Mescher M. F. Exogenous beta 2-microglobulin is required for antigenic peptide binding to isolated class I major histocompatibility complex molecules. Eur J Immunol. 1991 Sep;21(9):2289–2292. doi: 10.1002/eji.1830210945. [DOI] [PubMed] [Google Scholar]
  12. Kaul S., Fishbein M. C., Siegel R. J. Cardiac manifestations of acquired immune deficiency syndrome: a 1991 update. Am Heart J. 1991 Aug;122(2):535–544. doi: 10.1016/0002-8703(91)91013-d. [DOI] [PubMed] [Google Scholar]
  13. Madden D. R., Gorga J. C., Strominger J. L., Wiley D. C. The structure of HLA-B27 reveals nonamer self-peptides bound in an extended conformation. Nature. 1991 Sep 26;353(6342):321–325. doi: 10.1038/353321a0. [DOI] [PubMed] [Google Scholar]
  14. Moore M. W., Carbone F. R., Bevan M. J. Introduction of soluble protein into the class I pathway of antigen processing and presentation. Cell. 1988 Sep 9;54(6):777–785. doi: 10.1016/s0092-8674(88)91043-4. [DOI] [PubMed] [Google Scholar]
  15. Ng K. K., Vane J. R. Fate of angiotensin I in the circulation. Nature. 1968 Apr 13;218(5137):144–150. doi: 10.1038/218144a0. [DOI] [PubMed] [Google Scholar]
  16. Plummer T. H., Jr, Ryan T. J. A potent mercapto bi-product analogue inhibitor for human carboxypeptidase N. Biochem Biophys Res Commun. 1981 Jan 30;98(2):448–454. doi: 10.1016/0006-291x(81)90860-3. [DOI] [PubMed] [Google Scholar]
  17. Rock K. L., Gamble S., Rothstein L., Benacerraf B. Reassociation with beta 2-microglobulin is necessary for Db class I major histocompatibility complex binding of an exogenous influenza peptide. Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):301–304. doi: 10.1073/pnas.88.1.301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Rock K. L., Gamble S., Rothstein L. Presentation of exogenous antigen with class I major histocompatibility complex molecules. Science. 1990 Aug 24;249(4971):918–921. doi: 10.1126/science.2392683. [DOI] [PubMed] [Google Scholar]
  19. Rock K. L., Rothstein L. E., Gamble S. R., Benacerraf B. Reassociation with beta 2-microglobulin is necessary for Kb class I major histocompatibility complex binding of exogenous peptides. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7517–7521. doi: 10.1073/pnas.87.19.7517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Rötzschke O., Falk K., Deres K., Schild H., Norda M., Metzger J., Jung G., Rammensee H. G. Isolation and analysis of naturally processed viral peptides as recognized by cytotoxic T cells. Nature. 1990 Nov 15;348(6298):252–254. doi: 10.1038/348252a0. [DOI] [PubMed] [Google Scholar]
  21. Schumacher T. N., De Bruijn M. L., Vernie L. N., Kast W. M., Melief C. J., Neefjes J. J., Ploegh H. L. Peptide selection by MHC class I molecules. Nature. 1991 Apr 25;350(6320):703–706. doi: 10.1038/350703a0. [DOI] [PubMed] [Google Scholar]
  22. Semple J. W., Ellis J., Delovitch T. L. Processing and presentation of insulin. II. Evidence for intracellular, plasma membrane-associated and extracellular degradation of human insulin by antigen-presenting B cells. J Immunol. 1989 Jun 15;142(12):4184–4193. [PubMed] [Google Scholar]
  23. Staerz U. D., Karasuyama H., Garner A. M. Cytotoxic T lymphocytes against a soluble protein. Nature. 1987 Oct 1;329(6138):449–451. doi: 10.1038/329449a0. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Takahashi H., Houghten R., Putney S. D., Margulies D. H., Moss B., Germain R. N., Berzofsky J. A. Structural requirements for class I MHC molecule-mediated antigen presentation and cytotoxic T cell recognition of an immunodominant determinant of the human immunodeficiency virus envelope protein. J Exp Med. 1989 Dec 1;170(6):2023–2035. doi: 10.1084/jem.170.6.2023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Van Bleek G. M., Nathenson S. G. Isolation of an endogenously processed immunodominant viral peptide from the class I H-2Kb molecule. Nature. 1990 Nov 15;348(6298):213–216. doi: 10.1038/348213a0. [DOI] [PubMed] [Google Scholar]
  27. Vitiello A., Potter T. A., Sherman L. A. The role of beta 2-microglobulin in peptide binding by class I molecules. Science. 1990 Dec 7;250(4986):1423–1426. doi: 10.1126/science.2124002. [DOI] [PubMed] [Google Scholar]
  28. Widmann C., Maryanski J. L., Romero P., Corradin G. Differential stability of antigenic MHC class I-restricted synthetic peptides. J Immunol. 1991 Dec 1;147(11):3745–3751. [PubMed] [Google Scholar]

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