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Artificial antigen-presenting cells as a tool to exploit the immune `synapse'

Abstract

Recent progress in molecular medicine has provided important tools to identify antigen-specific T cells. In most cases, the approach is based on oligomeric combinations of recombinant major histocompatibility complex–peptide complexes fixed to various rigid supports available for binding by the T-cell receptor1,2,3,4,5,6,7,8. These tools have greatly increased our insight into mechanisms of immune responses mediated by CD8+ T cells1,2. Examples of the diverse fields of application for this technology include immunization, viral infections and oral tolerance induction1,2,3,4,5,6.

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Figure 1: Identification of antigen-specific cells with T-cell capture in a monoclonal TCR population.
Figure 2: Identification by T-cell capture of class II-restricted antigen-specific mouse T cells after immunization.
Figure 3: Interaction of aAPC with T cells induces membrane capping.

References

  1. Altman, J.D. et al. Phenotypic analysis of antigen-specific T lymphocytes. Science 274, 94–96 (1996).

    Article  CAS  Google Scholar 

  2. Davis, M.M. et al. Ligand recognition by alpha beta T-cell receptors. Annu. Rev. Immunol. 16, 523–544 (1998).

    Article  CAS  Google Scholar 

  3. Lee, P.P. et al. Characterization of circulating T cells specific for tumor-associated antigens in melanoma patients. Nature Med. 5, 677–854 (1999).

    Article  CAS  Google Scholar 

  4. Kirsten, J. et al. Virus-specific CD8+ T cells in primary and secondary influenza pneumonia. Immunity 8, 683–691 (1998).

    Article  Google Scholar 

  5. Mutis, T. et al. Tetrameric HLA class I-minor histocompatibility antigen peptide complexes demonstrate minor histocompatibility antigen-specific cytotoxic T lymphocytes in patients with graft-versus-host disease. Nature Med. 5, 839–842 (1999).

    Article  CAS  Google Scholar 

  6. Greten, T. et al. Direct visualization of antigen-specific T cells: HTLV-1-specific CD8+ T cells are activated in peripheral blood and accumulate in CSF from HAM/TSP patients. Proc. Natl. Acad. Sci. USA 95, 7568–7573 (1998).

    Article  CAS  Google Scholar 

  7. Lusembourg, A.T. et al. Biomagnetic isolation of antigen-specific CD8+ T cells usable in immunotherapy. Nature Biotechnol. 16, 281–285 (1998).

    Article  Google Scholar 

  8. Crawford, F., Kozono, H., White, J., Marrack, P. & Kappler, J. Detection of antigen-specific T cells with multivalent soluble class II MHC covalent peptide complexes. Immunity 8, 675–682 (1998).

    Article  CAS  Google Scholar 

  9. Grakoui, A. et al. The immunological synapse: A molecular machine controlling T-cell activation. Science 285, 221–227 (1999).

    Article  CAS  Google Scholar 

  10. Albani, S. et al. Positive selection in autoimmunity: Abnormal immune responses to a bacterial dnaJ antigenic determinant in patients with early rheumatoid arthritis. Nature Med. 1, 448–452 (1995).

    Article  CAS  Google Scholar 

  11. La Cava, A. et al. Genetic bias in immune responses to a cassette shared by different microorganisms in patients with rheumatoid arthritis. J. Clin. Invest. 100, 658–663 (1997).

    Article  CAS  Google Scholar 

  12. Anderson, D.E. et al. Weak peptide agonists reveal functional differences in B7–1 and B7-2 costimulation of human T-cell clones. J. Immunol. 159, 1669–1675 (1997).

    CAS  PubMed  Google Scholar 

  13. Nanda, N.K. & Sercarz, E.E. Induction of anti-self-immunity to cure cancer. Immunol. Today 19, 495–498 (1998).

    Article  Google Scholar 

  14. Moalem, G. et al. Autoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy. Nature Med. 5, 49–55 (1999).

    Article  CAS  Google Scholar 

  15. Brian, L. et al. Use of soluble peptide–DR4 tetramers to detect synovial T cells specific for cartilage antigen in patients with rheumatoid arthritis. Proc. Natl. Acad. Sci. USA 97, 291–296 (2000).

    Article  Google Scholar 

  16. Rees, W. et al. An inverse relationship between T-cell receptor affinity and antigen dose during CD4(+) T-cell responses in vivo and in vitro. Proc. Natl. Acad. Sci. USA 96, 9781–9786 (1999).

    Article  CAS  Google Scholar 

  17. Janssen, E.M. et al. Modulation of Th2 responses by peptide analogues in a murine model of the disease process depends on the Th1 or Th2 skewing characteristics of the therapeutic peptide. J. Immunol. 164, 580–588 (2000).

    Article  CAS  Google Scholar 

  18. Bonnin, D. et al. Ontogeny of synonymous T cell populations with specificity for a self MHC epitope mimicked by a bacterial homologue: an antigen-specific T cell analysis in a non-transgenic system. Eur. J. Immunol. 29, 3826–3836 (1999).

    Article  CAS  Google Scholar 

  19. Barton, G.M. & Rudensky, A.Y. Requirement for diverse, low-abundance peptides in positive selection of T cells. Science 283, 67–70 (1999).

    Article  CAS  Google Scholar 

  20. Viola, A., Schroeder, S., Sakakibara, Y. & Lanzavecchia, A. T lymphocyte costimulation mediated by reorganization of membrane microdomains. Science 283, 680–682 (1999).

    Article  CAS  Google Scholar 

  21. Sette, A. et al. Effect of pH on MHC class II-peptide interactions. J. Immunol. 148, 844–851 (1992).

    CAS  PubMed  Google Scholar 

  22. Van Rensen, A.J.M.L., Wauben, M.H.M., Grosfeld-Stulemeyer, M.C., Van Eden, W. & Crommelin, D.J.A. Liposomes with incorporated MHC class II/peptide complexes as antigen presenting vesicles for specific T-cell activation. Pharm. Res. 16, 198–204 (1999).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank D. Bonnin, D. Schuijffel, S. Nijenhuis and E. Quintela for technical support and assistance. We also thank Nicole Lewon for assistance in editing the manuscript. This study was supported in part by grants NO1-AR40770, NO1-AR44850, NO1-AR72232, NO1-AR41897 and NO1-AR92241. B.P. is supported by the `Ter Meulenfonds' of the Royal Netherlands Academy of Arts and Sciences and by the Dutch Rheumatoid Arthritis Foundation. M.W. is supported by a fellowship from the Royal Netherlands Academy of Arts and Sciences.

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Correspondence to Salvatore Albani.

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Prakken, B., Wauben, M., Genini, D. et al. Artificial antigen-presenting cells as a tool to exploit the immune `synapse'. Nat Med 6, 1406–1410 (2000). https://doi.org/10.1038/82231

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