Abstract
Any effect of serum on the antigenicity of peptides is potentially relevant to their use as immunogens in vivo. Here we demonstrate that serum contains distinct proteases that can increase or decrease the antigenicity of peptides. By using a functional assay, we show that a serum component other than beta 2-microglobulin enhances the presentation of ovalbumin peptides produced by cyanogen bromide cleavage. Three features of this serum activity implicate proteolysis: it is temperature dependent, it results in increased antigenicity in a low molecular weight peptide fraction, and it is inhibited by the protease inhibitor leupeptin. Conversely, presentation of the synthetic peptide OVA-(257-264) is inhibited by serum. This inhibition is unaffected by leupeptin but is blocked by bestatin, a protease inhibitor with distinct substrate specificities. Implications for peptide-based vaccine design and immunotherapy are discussed.
Full text
PDF



Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bevan M. J. Immunology. Stimulating killer cells. Nature. 1989 Nov 30;342(6249):478–479. doi: 10.1038/342478a0. [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]
- Elliott T., Cerundolo V., Elvin J., Townsend A. Peptide-induced conformational change of the class I heavy chain. Nature. 1991 May 30;351(6325):402–406. doi: 10.1038/351402a0. [DOI] [PubMed] [Google Scholar]
- Falk K., Rötzschke O., Stevanović S., Jung G., Rammensee H. G. Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules. Nature. 1991 May 23;351(6324):290–296. doi: 10.1038/351290a0. [DOI] [PubMed] [Google Scholar]
- Falo L. D., Jr, Sullivan K., Benacerraf B., Mescher M. F., Rock K. L. Analysis of antigen presentation by metabolically inactive accessory cells and their isolated membranes. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6647–6651. doi: 10.1073/pnas.82.19.6647. [DOI] [PMC free article] [PubMed] [Google Scholar]
- GORER P. A., AMOS D. B. Passive immunity in mice against C57BL leukosis E.L. 4 by means of iso-immune serum. Cancer Res. 1956 May;16(4):338–343. [PubMed] [Google Scholar]
- 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]
- Kozlowski S., Corr M., Takeshita T., Boyd L. F., Pendleton C. D., Germain R. N., Berzofsky J. A., Margulies D. H. Serum angiotensin-1 converting enzyme activity processes a human immunodeficiency virus 1 gp160 peptide for presentation by major histocompatibility complex class I molecules. J Exp Med. 1992 Jun 1;175(6):1417–1422. doi: 10.1084/jem.175.6.1417. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kozlowski S., Takeshita T., Boehncke W. H., Takahashi H., Boyd L. F., Germain R. N., Berzofsky J. A., Margulies D. H. Excess beta 2 microglobulin promoting functional peptide association with purified soluble class I MHC molecules. Nature. 1991 Jan 3;349(6304):74–77. doi: 10.1038/349074a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Perkins D. L., Lai M. Z., Smith J. A., Gefter M. L. Identical peptides recognized by MHC class I- and II-restricted T cells. J Exp Med. 1989 Jul 1;170(1):279–289. doi: 10.1084/jem.170.1.279. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Puri J., Factorovich Y. Selective inhibition of antigen presentation to cloned T cells by protease inhibitors. J Immunol. 1988 Nov 15;141(10):3313–3317. [PubMed] [Google Scholar]
- 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]
- 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]
- Rock K. L., Rothstein L., Gamble S. Generation of class I MHC-restricted T-T hybridomas. J Immunol. 1990 Aug 1;145(3):804–811. [PubMed] [Google Scholar]
- Sherman L. A., Burke T. A., Biggs J. A. Extracellular processing of peptide antigens that bind class I major histocompatibility molecules. J Exp Med. 1992 May 1;175(5):1221–1226. doi: 10.1084/jem.175.5.1221. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shimonkevitz R., Kappler J., Marrack P., Grey H. Antigen recognition by H-2-restricted T cells. I. Cell-free antigen processing. J Exp Med. 1983 Aug 1;158(2):303–316. doi: 10.1084/jem.158.2.303. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Takahashi H., Cease K. B., Berzofsky J. A. Identification of proteases that process distinct epitopes on the same protein. J Immunol. 1989 Apr 1;142(7):2221–2229. [PubMed] [Google Scholar]
- 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]
- Watson J. Continuous proliferation of murine antigen-specific helper T lymphocytes in culture. J Exp Med. 1979 Dec 1;150(6):1510–1519. doi: 10.1084/jem.150.6.1510. [DOI] [PMC free article] [PubMed] [Google Scholar]
- White J., Haskins K. M., Marrack P., Kappler J. Use of I region-restricted, antigen-specific T cell hybridomas to produce idiotypically specific anti-receptor antibodies. J Immunol. 1983 Mar;130(3):1033–1037. [PubMed] [Google Scholar]
- 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]