Abstract
Enumeration and analysis of antigen-specific T cells play a central role in tumor immunology. Recently a number of different methods have been developed to analyze antigen-specific T cell responses. MHC-Ig dimeric molecules were developed for detection and analysis of antigen specific T cells. Using, Ig as a molecular scaffold, dimeric MHC molecules bind stably to the corresponding T cells due to their increased avidity for the T cell receptor and can be used to identify peptide specific T cells by flow cytometry. In addition, this technique can be combined with functional assays analyzing peptide specific cytokine release and functional state of the T cells. Finally MHC-Ig dimers have been used in a variety of experiments to stimulate and amplify antigen specific T cells.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Dal Porto J., Johansen T.E., Catipovic B., et al. A soluble divalent class I major histocompatibility complex molecule inhibits alloreactive T cells at nanomolar concentrations. Proc Natl Acad Sci U S A. 1993;90(14):6671–6675.
Greten T.F., Slansky J.E., Kubota R., et al. Direct visualization of antigen-specific T cells: HTLV-1 Tax11-19-specific CD8(+) T cells are activated in peripheral blood and accumulate in cerebrospinal fluid from HAM/TSP patients. Proc Natl Acad Sci U S A. 1998;95(13):7568–7573.
Weigert M.G., Cesari I.M., Yonkovich S.J., Cohn M. Variability in the lambda light chain sequences of mouse antibody. Nature. Dec 12 1970;228(276):1045–1047.
Schneck J.P., Slansky J., O’Herrin S., Greten T.F. Use of MHC-Ig Dimers for Visualizing Antigen Specific T cells. Current Protocol in Immunology. New York: John Wiley & Sons Inc.; 1999:17.13.
Greten T.F., Korangy F., Neumann G., et al. Peptide-beta2-microglobulin-MHC fusion molecules bind antigen-specific T cells and can be used for multivalent MHC-Ig complexes. J Immunol Methods. Dec 20 2002;271(1–2):125–135.
O’Herrin S.M., Slansky J.E., Tang Q., et al. Antigen-specific blockade of T cells in vivo using dimeric MHC peptide. J Immunol. 2001;167(5):2555–2560.
Kalandadze A., Galleno M., Foncerrada L., Strominger J.L., Wucherpfennig K.W. Expression of recombinant HLA-DR2 molecules. Replacement of the hydrophobic transmembrane region by a leucine zipper dimerization motif allows the assembly and secretion of soluble DR alpha beta heterodimers. J Biol Chem. 1996;271(33):20156–20162.
Casares S., Bona C.A., Brumeanun T.D. Engineering and characterization of a murine MHC class II-immunoglobulin chimera expressing an immunodmoinant CD4 T viral epitope. Protein Engineering. 1997;10:1295–1301.
Lebowitz M.S., O’Herrin S.M., Hamad A.R., et al. Soluble, high-affinity dimers of T cell receptors and class II major histocompatibility complexes: biochemical probes for analysis and modulation of immune responses. Cellular Immunology. 1999;192(2):175–184.
Casares S., Stan A.C., Bona C.A., Brumeanu T.D. Antigen-specific downregulation of T cells by doxorubicin delivered through a recombinant MHC II—peptide chimera. Nat Biotechnol. 2001;19(2):142–147.
Hamad A.R,. O’Herrin S.M., Lebowitz M.S., et al. Potent T cell activation with dimeric peptide-major histocompatibility complex class II ligand: the role of CD4 coreceptor. Journal of Experimental Medicine. 1998;188(9):1633–1640.
Casares S., Zong C.S., Radu D.L., Miller A., Bona C.A., Brumeanu T.D. Antigenspecific signaling by a soluble, dimeric peptide/major histocompatibility complex class II/Fc chimera leading to T helper cell type 2 differentiation. J Exp Med. 1999;190(4):543–553.
Appel H., Gauthier L., Pyrdol J., Wucherpfennig K.W. Kinetics of T-cell receptor binding by bivalent HLA-DR. Peptide complexes that activate antigen-specific human T-cells. J Biol Chem. 2000;275(1):312–321.
Masteller E.L., Warner M.R., Ferlin W., et al. Peptide-MHC class II dimers as therapeutics to modulate antigen-specific T cell responses in autoimmune diabetes. J Immunol. Nov 15 2003;171(10):5587–5595.
Nagai M., Kubota R., Greten T.F., Schneck J.P., Leist T.P., Jacobson S. Increased activated human T cell lymphotropic virus type I (HTLV-I) Tax11-19-specific memory and effector CD8+ cells in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis: correlation with HTLV-I provirus load. J Infect Dis. Jan 15 2001;183(2):197–205.
Bieganowska K., Hollsberg P., Buckle G.J., et al. Direct analysis of viral-specific CD8+ T cells with soluble HLA-A2/Tax11-19 tetramer complexes in patients with human T cell lymphotropic virus-associated myelopathy. Journal of Immunology. 1999;162(3):1765–1771.
Carruth L.M., Greten T.F., Murray C.E., et al. An algorithm for evaluating human cytotoxic T lymphocyte responses to candidate AIDS vaccines. AIDS Res Hum Retroviruses. Jul 20 1999;15(11):1021–1034.
La Rosa C., Krishnan R., Markel S., et al. Enhanced immune activity of cytotoxic T-lymphocyte epitope analogs derived from positional scanning synthetic combinatorial libraries. Blood. 2001;97(6):1776–1786.
Howard M.C., Spack E.G., Choudhury K., Greten T.F., Schneck J.P. MHC-based diagnostics and therapeutics-clinical applications for disease-linked genes. Immunol Today. Apr 1999;20(4):161–165.
Märten A., Greten T., Ziske C., et al. Generation of activated and antigen-specific T cells with cytotoxic activity after co-culture with dendritic cells. Cancer Immunol Immunother. Mar 2002;51(1):25–32.
Walker E.B., Haley D., Miller W., et al. gp100(209-2M) peptide immunization of human lymphocyte antigen-A2+ stage I-III melanoma patients induces significant increase in antigen-specific effector and long-term memory CD8+ T cells. Clin Cancer Res. Jan 15 2004;10(2):668–680.
Hu H.M., Dols A., Meijer S.L., et al. Immunological monitoring of patients with melanoma after peptide vaccination using soluble peptide/HLA-A2 dimer complexes. J Immunother. Jan–Feb 2004;27(1):48–59.
Slansky J.E., Rattis F.M., Boyd L.F., et al. Enhanced Antigen-Specific Antitumor Immunity with Altered Peptide Ligands that Stabilize the MHC-Peptide-TCR Complex. Immunity. 2000;13(4):529–538.
Huang A.Y., Gulden P.H., Woods A.S., et al. The immunodominant major histocompatibility complex class I-restricted antigen of a murine colon tumor derives from an endogenous retroviral gene product. Proc Natl Acad Sci U S A. 1996;93(18):9730–9735.
Selin L.K., Lin M.Y., Kraemer K.A., et al. Attrition of T cell memory: selective loss of LCMV epitope-specific memory CD8 T cells following infections with heterologous viruses. Immunity. 1999;11(6):733–742.
Oelke M., Maus M.V., Didiano D,. June C.H., Mackensen A., Schneck J.P. Ex vivo induction and expansion of antigen-specific cytotoxic T cells by HLA-Ig-coated artificial antigen-presenting cells. Nat Med. May 2003;9(5):619–624.
Fahmy T.M., Bieler J.G., Edidin M., Schneck J.P. Increased TCR avidity after T cell activation: a mechanism for sensing low-density antigen. Immunity. Feb 2001;14(2):135–143.
Eichmann K., Falk I., Melchers I., Simon M.M. Quantitative studies on T cell diversity. I. Determination of the precursor frequencies for two types of streptococcus A-specific helper cells in nonimmune, polyclonally activated splenic T cells. J Exp Med. 1980;152(3):477–492.
Greten T.F, Schneck J.P. Development and use of multimeric major histocompatibility complex molecules. Clin Diagn Lab Immunol. Mar 2002;9(2):216–220.
Murali-Krishna K., John D., Altman J.D., et al. Counting Antigen-Specific CD8 T Cells: A Reevaluation of Bystander Activation during Viral Infection. Immunity. 1998;8:177–187.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2005 Springer
About this chapter
Cite this chapter
Greten, T.F., Korangy, F. (2005). MHC-Ig Dimeric Molecules. In: Nagorsen, D., Marincola, F. (eds) Analyzing T Cell Responses. Springer, Dordrecht. https://doi.org/10.1007/1-4020-3623-X_13
Download citation
DOI: https://doi.org/10.1007/1-4020-3623-X_13
Publisher Name: Springer, Dordrecht
Print ISBN: 978-1-4020-3622-4
Online ISBN: 978-1-4020-3623-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)