Melenhorst, Jan Joseph, 1965-, Scheinberg, Phillip, Chattopadhyay, Pratip K., Lissina, Anna, Gostick, Emma, Cole, David K., Wooldridge, L. (Linda), Berg, Hugo van den, 1968-, Bornstein, Ethan, Hensel, Nancy F., Douek, Daniel, Roederer, Mario, Sewell, Andrew K., Barrett, A. John and Price, D. A. (David A.). (2008) Detection of low avidity CD8(+) T cell populations with coreceptor-enhanced peptide-major histocompatibility complex class I tetramers. Journal of Immunological Methods, Vol.338 (No.1-2). pp. 31-39. ISSN 0022-1759

Full text not available from this repository.

Abstract

The development of soluble recombinant peptide-major histocompatibility complex class I (pMHCI) molecules conjugated in multimeric form to fluorescent labels has enabled the physical quantification and characterization of antigen-specific CD8(+) T cell populations by flow cytometry. Several factors determine the binding threshold that enables visualization of cognate CD8(+) T cells with these reagents; these include the affinity of the T cell receptor (TCR) for pMHCl antigen. Here, we show that multimers constructed from peptide-human leukocyte antigen (pHLA) A*0201 monomers engineered in the heavy chain alpha 2 domain to enhance CD8 binding (K-D approximate to 85 mu M) without impacting the TCR binding platform can detect cognate CD8(+) T cells bearing low affinity TCRs that are not visible with the corresponding wildtype pHLA A*0201 multimeric complexes. Mechanistically, this effect is mediated by a disproportionate enhancement of the TCR/pMHCl association rate. In direct ex vivo applications, these coreceptor-enhanced multimers exhibit faithful cognate binding properties; concomitant increases in background staining within the non-cognate CD8(+) T cell population can be resolved phenotypically using polychromatic flow cytometry as a mixture of naive and memory cells. These findings provide the first validation of a novel approach to the physical detection of low avidity antigen-specific CD8(+) T cell populations; such coreceptor-enhanced multimeric reagents are likely to be useful in a multitude of settings for the detection of auto-immune, tumor-specific and cross-reactive CD8(+) T cells. (C) 2008 Elsevier B.V. All rights reserved.

Item Type:	Journal Article
Subjects:	Q Science > QD Chemistry Q Science > QH Natural history > QH301 Biology Q Science > QR Microbiology > QR180 Immunology
Divisions:	Faculty of Science > Mathematics Faculty of Science > Centre for Systems Biology
Library of Congress Subject Headings (LCSH):	Major histocompatibility complex, Flow cytometry, T cells
Journal or Publication Title:	Journal of Immunological Methods
Publisher:	Elsevier BV
ISSN:	0022-1759
Date:	30 September 2008
Volume:	Vol.338
Number:	No.1-2
Number of Pages:	9
Page Range:	pp. 31-39
Identification Number:	10.1016/j.jim.2008.07.008
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Funder:	National Institutes of Health (U.S.) (NIH), National Institute of Allergy and Infectious Diseases (U.S.). Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (U.S.) (NIAID), National Heart, Lung, and Blood Institute (NHLBI), Medical Research Council (Great Britain) (MRC), Wellcome Trust (London, England)
References:	Altman, J.D., et al., 1996. Phenotypic analysis of antigen-specific T lymphocytes. Science 274, 94. Boulter, J.M., et al., 2003. Stable, soluble T-cell receptor molecules for crystallization and therapeutics. Protein Eng. 16, 707. Cho, B.K., Rao, V.P., Ge, Q., Eisen, H.N., Chen, J., 2000. Homeostasis-stimulated proliferation drives naive T cells to differentiate directly into memory T cells. J. Exp. Med. 192, 549. Choi, E.M., et al., 2003. High avidity antigen-specific CTL identified by CD8- independent tetramer staining. J. Immunol. 171, 5116. Cole, D.K., et al., 2007. Human TCR-binding affinity is governed by MHC class restriction. J. Immunol. 178, 5727. Diamond, D.J., York, J., Sun, J.Y., Wright, C.L., Forman, S.J., 1997. Development of a candidate HLA A⁎0201 restricted peptide-based vaccine against human cytomegalovirus infection. Blood 90, 1751. Douek, D.C., et al., 2002. A novel approach to the analysis of specificity, clonality, and frequency of HIV-specific T cell responses reveals a potential mechanism for control of viral escape. J. Immunol. 168, 3099. Gagnon, S.J., et al., 2006. T cell receptor recognition via cooperative conformational plasticity. J. Mol. Biol. 363, 228. Gakamsky, D.M., et al., 2005. CD8 kinetically promotes ligand binding to the T-cell antigen receptor. Biophys. J. 89, 2121. Gao, G.F., et al., 1997. Crystal structure of the complex between human CD8alpha(alpha) and HLA-A2. Nature 387, 630. Gao, L., et al., 2000. Selective elimination of leukemic CD34(+) progenitor cells by cytotoxic T lymphocytes specific for WT1. Blood 95, 2198. Goldrath, A.W., Bevan, M.J., 1999. Low-affinity ligands for the TCR drive proliferation of mature CD8+ T cells in lymphopenic hosts. Immunity 11, 183. Hutchinson, S.L., et al., 2003. The CD8 T cell coreceptor exhibits disproportionate biological activity at extremely low binding affinities. J. Biol. Chem. 278, 24285. Kasprowicz, V., et al., 2008. Defining the directionality and quality of influenza virus-specific CD8+ T cell cross-reactivity in individuals infected with hepatitis C virus. J. Clin. Invest. 118, 1143. Klenerman, P., Cerundolo, V., Dunbar, P.R., 2002. Tracking T cells with tetramers: new tales from new tools. Nat. Rev. Immunol. 2, 263. Krupica Jr., T., Fry, T.J., Mackall, C.L., 2006. Autoimmunity during lymphopenia: a two-hit model. Clin. Immunol. 120, 121. Laugel, B., et al., 2005. Design of soluble recombinant T cell receptors for antigen targeting and T cell inhibition. J. Biol. Chem. 280, 1882. Laugel, B., et al., 2007. Different T cell receptor affinity thresholds and CD8 coreceptor dependence govern cytotoxic T lymphocyte activation and tetramer binding properties. J. Biol. Chem. 282, 23799. Lee, P.P., et al., 1999. Characterization of circulating T cells specific for tumorassociated antigens in melanoma patients. Nat. Med. 5, 677. Lyons, G.E., et al., 2006. T-cell receptor tetramer binding or the lack there of does not necessitate antigen reactivity in T-cell receptor transduced T cells. Cancer Immunol. Immunother. 55, 1142. Molldrem, J., et al., 1996. Targeted T-cell therapy for human leukemia: cytotoxic T lymphocytes specific for a peptide derived from proteinase 3 preferentially lyse human myeloid leukemia cells. Blood 88, 2450. Molldrem, J.J., et al., 2003. Chronic myelogenous leukemia shapes host immunity by selective deletion of high-avidity leukemia-specific T cells. J. Clin. Invest. 111, 639. Oka, Y., et al., 2000. Human cytotoxic T-lymphocyte responses specific for peptides of the wild-type Wilms' tumor gene (WT1) product. Immunogenetics 51, 99. Perfetto, S.P., et al., 2006. Amine reactive dyes: an effective tool to discriminate live and dead cells in polychromatic flowcytometry. J. Immunol. Methods 313, 199. Pittet, M.J., et al., 2003. alpha3 domain mutants of peptide/MHC class I multimers allow the selective isolation of high avidity tumor-reactive CD8 T cells. J. Immunol. 171, 1844. Price, D.A., et al., 2004. T cell receptor recognition motifs govern immune escape patterns in acute SIV infection. Immunity 21, 793. Price, D.A., et al., 2005. Avidity for antigen shapes clonal dominance in CD8+ T cell populations specific for persistent DNA viruses. J. Exp. Med. 202, 1349. Purbhoo, M.A., et al., 2001. The human CD8 coreceptor effects cytotoxic T cell activation and antigen sensitivity primarily by mediating complete phosphorylation of the Tcell receptor zeta chain. J. Biol. Chem. 276, 32786. Purbhoo, M.A., et al., 2007. The HLA A⁎0201-restricted hTERT(540–548) peptide is not detected on tumor cells by a CTL clone or a high-affinity T-cell receptor. Mol. Cancer Ther. 6, 2081. Rubio-Godoy, V., et al., 2001. Discrepancy between ELISPOT IFN-gamma secretion and binding of A2/peptide multimers to TCR reveals interclonal dissociation of CTL effector function from TCR-peptide/MHC complexes half-life. Proc. Natl. Acad. Sci. U S A 98, 10302. Selin, L.K., et al., 2006. Memory of mice and men: CD8+ T-cell cross-reactivity and heterologous immunity. Immunol. Rev. 211, 164. van den Berg, H.A., Wooldridge, L., Laugel, B., Sewell, A.K., 2007. Coreceptor CD8-driven modulation of T cell antigen receptor specificity. J. Theor. Biol. 249, 395. Whelan, J.A., et al., 1999. Specificity of CTL interactions with peptide-MHC class I tetrameric complexes is temperature dependent. J. Immunol. 163, 4342. Wooldridge, L., et al., 2005. Interaction between the CD8 coreceptor and major histocompatibility complex class I stabilizes T cell receptor– antigen complexes at the cell surface. J. Biol. Chem. 280, 27491. Wooldridge, L., et al., 2007. Enhanced immunogenicity of CTL antigens through mutation of the CD8 binding MHC class I invariant region. Eur. J. Immunol. 37, 1323. Wyer, J.R., et al., 1999. T cell receptor and coreceptor CD8 alphaalpha bind peptide-MHC independently and with distinct kinetics. Immunity 10, 219. Zippelius, A., et al., 2004. Effector function of human tumor-specific CD8 T cells in melanoma lesions: a state of local functional tolerance. Cancer Res. 64, 2865.
URI:	http://wrap.warwick.ac.uk/id/eprint/29298

Data sourced from Thomson Reuters' Web of Knowledge

Request changes to a record

Actions (login required)

View Item