Abstract
T-cells specific for a particular antigen represent a small percentage of the overall T-cell population. Detecting the presence of antigen specific T-cells in patients, animal models or populations of cultured cells has presented a challenge to researchers. The T-cell capture method described here utilizes a truly artificial method of antigen presentation and requires only 50,000 cells for the detection of the major histomcompatibility complex (MHC) class II and antigen restricted T-cells. With this method, liposomes, prepared with readily available materials, are loaded with neutravidin “rafts” comprised of MHC/peptide complexes, anti-CD28, a costimulatory molecule, and anti-LFA-1, an adhesion molecule. These artificial APCs are easily manipulated to include any MHC, antibodies to cell surface markers and/or costimulatory signals of interest thereby enabling not only T-cell identification but also the manipulation of mechanisms of T-cell activation.
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References
Clark, D. M., Boylston, A. W., Hall, P. A., and Carrel, S. (1986) Antibodies to T cell antigen receptor beta chain families detect monoclonal T cell proliferation. Lancet. 2, 835–837.
Albani, S., Keystone, E. C., Nelson, J. L., et al. (1995) Positive selection in autoimmunity: abnormal immune responses to a bacterial dnaJ antigenic determinant in patients with early rheumatoid arthritis. Nat. Med. 1, 448–452.
Dustin, M. L., Miller, J. M., Ranganath, S., et al. (1996) TCR-mediated adhesion of T cell hybridomas to planar bilayers containing purified MHC class II/peptide complexes and receptor shedding during detachment. Immunol. 157, 2014–2021.
Klenerman, P., Cerundolo, V., and Dunbar, P. R. (2002) Tracking T cells with tetramers: new tales from new tools. Nat. Rev. Immunol. 2, 263–272.
Mallone, R. and Nepom, G.T. (2004) MHC Class II tetramers and the pursuit of antigen-specific T cells: define, deviate, delete. Clin. Immunol. 110, 232–242.
Mallet-Designe, V. I, Stratmann, T., Homann, D., Carbone, F., Oldstone, M. B., Teyton, L. (2003) Detection of low-avidity CD4+ T cells using recombinant artificial APC: following the antiovalbumin immune response. J. Immunol. 170, 123–131.
Kim, J. V., Latouche, J. B., Riviere, I,. and Sadelain, M. (2004) The ABCs of artificial antigen presentation. Nat. Biotechnol. 22, 403–410.
Rosenberg S. A., Yang J. C., and Restifo N. P. (2004) Cancer immunotherapy: moving beyond current vaccines. Nat. Med. 10, 909–915.
Dustin, M.L. (2004) Stop and go traffic to tune T cell responses. Immunity 21, 305–314.
Valitutti, S. and Lanzavecchia, A. (1997) Serial triggering of TCRs: a basis for the sensitivity and specificity of antigen recognition. Immunol. Today 18, 299–304.
Pentcheva-Hoang, T., Egen, J. G., Wojnoonski, K., and Allison, J. P. (2004) B7-1 and B7-2 selectively recruit CTLA-4 and CD28 to the immunological synapse. Immunity 21, 401–413.
Grakoui, A., Bromley, S. K., Sumen, C., et al. (1999) The immunological synapse: a molecular machine controlling T cell activation. Science 285, 221–227.
van Rensen A. J., Wauben M. H., Grosfeld-Stulemeyer M. C., van Eden W., and Crommelin D. J. (1999) Liposomes with incorporated MHC class II/peptide complexes as antigen presenting vesicles for specific T cell activation. Pharm. Res. 16, 198–204.
Jenkins, M. K., and Schwartz, R. H. (1987) Antigen presentation by chemically modified splenocytes induces antigen-specific T cell unresponsiveness in vitro and in vivo. J. Exp. Med. 165, 302–319.
Krogsgaard, M., Huppa, J. B., Purbhoo, M. A., and Davis, M. M. (2003) Linking molecular and cellular events in T-cell activation and synapse formation. Semin. Immunol. 15, 307–315.
Lee, K. H., Dinner, A. R., Tu, C et al. (2003) The immunological synapse balances T cell receptor signaling and degradation. Science 302, 1218–1222.
Prakken, B., Wauben, M., Genini, D., et al. (2000) Artificial antigen-presenting cells as a tool to exploit the immune “synapse.” Nat. Med. 6, 1406–1410.
Giannoni, F., Barnett, J., Bi, K., et al. (2004) Clustering of T cell ligands on aAPC membranes influences T cell activation and PKC theta translocation to the T cell plasma membrane. J. Immunology, in press.
Bonnin, D., Prakken, B., Samodal, R., La Cava, A., Carson, D. A., and Albani, S. (1999) Ontogeny of synonymous T cell populations with specificity for a self MHC epitope mimicked by a bacterial homologoue: an antigen-specific T cell analysis in a nontransgenic system. Eur. J. Immunol. 29, 3826–3836.
Massa, M., Costouros, N., Mazzoli, F., et al. (2002) Self epitopes shared between human skeletal myosin and Streptococcus pyogenes M5 protein are targets of immune responses in active juvenile dermatomyositis. Arthritis Rheum. 46, 3015–3025.
de Kleer, I. M., Wedderburn, L. R., Taams, L. S., et al. (2004) CD4+CD25bright regulatory T cells actively regulate inflammation in the joints of patients with the remitting form of juvenile idiopathic arthritis. J. Immunol. 172, 6435–6443.
Prakken, B. J., Samodal, R., Le, T. D., et al. (2004) Epitope-specific immunotherapy induces immune deviation of proinflammatory T cells in rheumatoid arthritis. Proc.Natl.Acad.Sci. USA. 101, 4228–4233.
Brian, A. A. and McConnell, H. M. (1984) Allogeneic stimulation of cytotoxic T cells by supported planar membranes. Proc.Natl.Acad.Sci. USA 81, 6159–6163.
Sidney, J., Southwood, S., Oseroff, C., del Guercio, M-F., Sette, A., and Grey, H. M. (1999) Ligand-Receptor Interactions in the Immune System. In: Current Methods in Immunology, Coligan, J. E., Kruisbell, A. M., Margulies, D. H., Shevach, E. M., and Strober, W., eds., New York: New York, pp. 18.3.1–18.3.18.
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Koffeman, E., Keogh, E., Klein, M., Prakken, B., Albani, S. (2007). Identification and Manipulation of Antigen Specific T-Cells with Artificial Antigen Presenting Cells. In: Cope, A.P. (eds) Arthritis Research. Methods in Molecular Medicine, vol 136. Humana Press. https://doi.org/10.1007/978-1-59745-402-5_6
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DOI: https://doi.org/10.1007/978-1-59745-402-5_6
Publisher Name: Humana Press
Print ISBN: 978-1-58829-918-5
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