iBet uBet web content aggregator. Adding the entire web to your favor.
iBet uBet web content aggregator. Adding the entire web to your favor.



Link to original content: https://doi.org/10.1038/nbt0398-281
Biomagnetic isolation of antigen-specific CD8+ T cells usable in immunotherapy | Nature Biotechnology
Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Article
  • Published:

Biomagnetic isolation of antigen-specific CD8+ T cells usable in immunotherapy

Nature Biotechnology volume 16, pages 281–285 (1998)Cite this article

Abstract

Isolating antigen-specific T lymphocytes is hampered by the low frequency of the cells and the low affinity between T-cell receptors (TCR) and antigen. We describe the isolation and purification of antigen-specific CD8+ T lymphocytes from mixed T-cell populations. Magnetic beads coated with major histocompatibility complex class I molecules loaded with specific peptide were used as a substrate for T-cell capture. Low-frequency T cells, as well as T cells with TCR of low affinity for the antigen were captured on the beads. Following isolation and expansion, recovered cells specifically killed target cells in vitro, and displayed antiviral effect in vivo.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Riddell, S.R., Watanabe, K.S., Goodrich, J.M., Li, C.R., Agha, M.E. and Greenberg, P.D. 1992. Restoration of viral immunity in immunodeficient humans by the adoptive transfer of T cell clones. Science 257: 238–241.

    Article  CAS  PubMed  Google Scholar 

  2. Lau, L.L., Jamieson, B.D., Somasundaram, T. and Ahmed, R. 1994. Cytotoxic T-cell memory without antigen. Nature 369: 648–652.

    Article  CAS  PubMed  Google Scholar 

  3. Hou, S., Hyland, L., Ryan, K.W., Portner, A. and Doherty, P.C. 1994. Virus-specific CD8+ T cell memory determined by clonal burst size. Nature 369: 652.

    Article  CAS  PubMed  Google Scholar 

  4. Snow, E.C., Vitetta, E.S. and Uhr, J.W. 1983. Activation of antigen-enriched B cells I. Purification and response to thymus-independent antigens. J. Immunol. 130: 607–613.

    CAS  PubMed  Google Scholar 

  5. Matsui, K., Boniface, J.J., Reay, P.A., Schild, H. Fazekas de St Groth, B., and Davis, M.M. 1991. Low affinity interaction of peptide-MHC complexes with T cell receptors. Science 254: 1788–1791.

    Article  CAS  PubMed  Google Scholar 

  6. Weber, S., Traunecker, A., Oliveri, F., Gerhard, W. and Karjalainen, K. 1992. Specific low-affinity recognition of major histocompatibility complex plus peptide by soluble T-cell receptor. Nature 356: 793–796.

    Article  CAS  PubMed  Google Scholar 

  7. Corr, M., Slanetz, A.E., Boyd, L.F., Jelonek, M.T., Khilko, S., al-Ramadi, B.K. et al. 1994. T cell receptor-MHC class I peptide interactions: affinity, kinetics, and specificity. Science 265: 946–949.

    Article  CAS  PubMed  Google Scholar 

  8. Sykulev, Y., Brunmark, A., Jackson, M., Cohen, R.J., Peterson, P.A. and Eisen, H.N. 1994. Kinetics and affinity of reactions between an antigen-specific T cell receptor and peptide-MHC complexes. Immunity 1: 15–22.

    Article  CAS  PubMed  Google Scholar 

  9. Sykulev, Y., Brunmark, A., Tsomides, T.J., Kageyama, S., Jackson, M., Peterson, P.A. and Eisen, H.N. 1994. High affinity reactions between antigen-specific T-cell receptors and peptides associated with allogeneic and syngeneic major histocompatibility complex class I proteins. Proc. Natl. Acad. Sci. USA 91: 11487–11491.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Radbruch, A. and Recktenwald, D. 1995. Detection and isolation of rare cells. Curr. Opin. Immunol. 7: 270–273.

    Article  CAS  PubMed  Google Scholar 

  11. Bellone, G., Geuna, M., Carbone, A., Silvestri, S., Foa, R., Emanuelli, G. and Matera, L. 1995. Regulatory action of prolactin on the in vitro growth of CD34+ve human hemopoietic progenitor cells. J. Cell. Physiol. 163: 221–231.

    Article  CAS  PubMed  Google Scholar 

  12. Jackson, M.R., Song, E.S. Yang, Y., and Peterson, P.A. 1992. Empty and pep-tide-containing conformers of class I major histocompatibility complex molecules expressed in Drosophila melanogaster cells. Proc. Natl. Acad. Sci. USA 89: 12117–12121.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Engelhard, V.H. 1994. Structure of peptides associated with class I molecules. Curr. Opin. Immunol. 6: 13–23.

    Article  CAS  PubMed  Google Scholar 

  14. Ramensee, H.G., Friede, T. and Stevanovic, S. 1995. MHC ligands and peptide motifs: first listing. Immunogenetics 41: 178–228.

    Article  Google Scholar 

  15. Nakanishi, M., Brian, A.A. and McConnell, H.M. 1983. Binding of cytotoxic T-lymphocytes to supported lipid monolayers containing trypsinized H-2K . Mol. Immunol. 20: 1227–1231.

    Article  CAS  PubMed  Google Scholar 

  16. De Bruijn, M.L.H., Nieland, J.D., Schumacher, T.N., Ploegh, H.L., Kast, W.M. and Melief, C.J. 1992. Mechanisms of induction of primary virus-specific cytotoxic T lymphocyte responses. Eur. J. Immunol. 22: 3013–3020.

    Article  CAS  PubMed  Google Scholar 

  17. Kane, K.P. and Mescher, M.F. 1993. Activation of CDS-dependent cytotoxic T lymphocyte adhesion and degranulation by peptide class I antigen complexes. J. Immunol. 150:4788–4797.

    CAS  PubMed  Google Scholar 

  18. Sha, W.C., Nelson, C.A., Newberry, R.D., Kranz, D.M., Russell, J.H. and Loh, D.Y. 1988. Selective expression of an antigen receptor on CDs-bearing T lymphocytes in transgenic mice. Nature 335: 271–274.

    Article  CAS  PubMed  Google Scholar 

  19. Tallquist, M.D. and Pease, L.R. 1995. Alloreactive 2C T cells recognize a self peptide in the context of the mutant Kbm3 molecule. J. Immunol. 155: 2419–2426.

    CAS  PubMed  Google Scholar 

  20. Tallquist, M.D., Yun, T.J. and Pease, L.R. 1996. A single T cell receptor recognizes structurally distinct MHC/peptide complexes with high specificity. J. Exp. Med. 814: 1017–1026.

    Article  Google Scholar 

  21. Udaka, K., Wiesmüller, K.H., Kienle, S., Jung, G. and Walden, P. 1996. Self-MHC-restricted peptides recognized by an alloreactive T lymphocyte clone. J. Immunol. 157: 670–678.

    CAS  PubMed  Google Scholar 

  22. Mescher, M.F. 1995. Molecular interactions in the activation of effector and precursor cytotoxic T lymphocytes. Immunol. Rev. 146: 177–210.

    Article  CAS  PubMed  Google Scholar 

  23. Cai, Z. and Sprent, J. 1996. Influence of antigen dose and costimulation on the primary response of CD8+ T cells in vitro. J. Exp. Med. 183: 2247–2257.

    Article  CAS  PubMed  Google Scholar 

  24. Speiser, D.E., Kyburz, D., Stübi, U., Hengartner, H. and Zinkernagel, R.M. 1992. Discrepancy between in vitro and in vivo virus neutralyzing cytotoxic T celf reactivities. J. Immunol. 149: 972–980.

    CAS  PubMed  Google Scholar 

  25. Dillon, S.R., Jameson, S.C. and Fink, P.J. 1994. Vβ5 + T cell receptors skew toward OVA+H-2Kb recognition. J. Immunol. 152: 1790–1801.

    CAS  PubMed  Google Scholar 

  26. Sawada, K., Kranz, S.B., Dai, C.H., Koury, S.T., Horn, S.T., Glick, A.D. and Civin, C.I. 1990. Purificatoion of human blood brust-forming units-erythroid and demonstration of the evolution of erythropoietin receptors. J. Cell. Physiol. 142: 219–230.

    Article  CAS  PubMed  Google Scholar 

  27. Kato, K. and Radbruch, A. 1993. Isolation and characterization of CD34+ hematopoietic stem cells from human peripheral blood by high-gradient magnetic cell sorting. Cytometry 14: 384–392.

    Article  CAS  PubMed  Google Scholar 

  28. Irsch, J., Irlenbusch, S., Radl, J., Burrows, P.O., Cooper, M.D. and Radbruch, A.H. 1994. Switch recombination in normal IgA,+ B lymphocytes. Proc. Natl. Acad. Sci. USA 91: 1323–1327.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Altman, J.D., Moss, P.A.H., Goulder, P.J.R., Barouch, D.H., McHeyzer-Williams, M.G., Bell, J.I. et al. 1996. Phenotypic analysis of antigen-specific T lymphocytes. Science 274: 94–96.

    Article  CAS  PubMed  Google Scholar 

  30. Hansen, T.H., Myers, N.B. and Lee, D.R. 1988. Studies of two antigenic forms of Ld with disparate β,-microglobulin (β2m) associations suggest that β2m facilitates the folding of the α1 and α2 domains during de novo synthesis. J. Immunol. 140: 3522–3527.

    CAS  PubMed  Google Scholar 

  31. Kranz, D.M., Tonegawa, S. and Eisen, H.N. 1984. Attachment of an anti-receptor antibody to non-target cells renders them susceptible to lysis by a clone of cytotoxic T lymphocytes. Proc. Natl. Acad. Sci. USA 81: 7922–7926.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Wunderlich, J. and Shearer, G. 1991. Induction and measurement of cytotoxic T lymphocyte activity, pp. 3.11.1.–3.11.15 in Current protocols in immunology. Coligan, J.E., Kruisbeek, A.M., Margulies, D.H., Shevach, E.M. and Strober, W. (eds.). John Wiley and Sons, New York, NY.

    Google Scholar 

  33. Byrne, J.A. and Oldstone, M.B.A. 1984. Biology of cloned cytotoxic T lymphocytes specific for lymphocytic choriomeningitis virus: clearance of virus in vivo. J. Virol. 51: 682–686.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Glantz, S.A. 1996. The special case of two groups: the t test, pp. 65–84 in Primer of biostatistics. McGraw-Hill, New York, NY.

    Google Scholar 

  35. Van der Most, R.G., Sette, A., Oseroff, C., Alexander, J., Murali-Krishna, K., Lau, L.L. et al. 1996. Analysis of cytotoxic T cell responses to dominant and subdom-inant epitopes during acute and chronic lymphocytic choriomeningitis virus infection. J. Immunol. 157: 5543–5554.

    CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Alain T. Luxembourg

    Present address: La Jolla Institute for Allergy and Immunology, San Diego, CA, 92121

  2. Persephone Borrow

    Present address: The Edward Jenner Institute for Vaccine Research, Compton, Newbury, Berkshire, RG20 7NN, UK

  3. Luc Teyton

    Present address: The Scripps Research Institute, La Jolla, CA, 92037

  4. Alain T. Luxembourg: e-mail: aluxembourg@liai.org

Authors and Affiliations

  1. R. W. Johnson Pharmaceutical Research Institute, San Diego, CA, 92121

    Anders B. Brunmark, Per A. Peterson & Michael R. Jackson

  2. The Scripps Research Institute, La Jolla, CA, 92037

    Persephone Borrow

Authors
  1. Alain T. Luxembourg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Persephone Borrow
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Luc Teyton
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anders B. Brunmark
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Per A. Peterson
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Michael R. Jackson
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Luxembourg, A., Borrow, P., Teyton, L. et al. Biomagnetic isolation of antigen-specific CD8+ T cells usable in immunotherapy. Nat Biotechnol 16, 281–285 (1998). https://doi.org/10.1038/nbt0398-281

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nbt0398-281

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing