Skip to main content

Tools and Methods for Identification and Analysis of Rare Antigen-Specific T Lymphocytes

  • Chapter
  • First Online:
T Lymphocytes as Tools in Diagnostics and Immunotoxicology

Part of the book series: Experientia Supplementum ((EXS,volume 104))

Abstract

T lymphocytes are essential as effector and memory cells for immune defense against infections and as regulatory T cells in the establishment and maintenance of immune tolerance. However, they are also involved in immune pathology being effectors in autoimmune and allergic diseases or suppressors of immunity in cancer, and they often cause problems in transplantation. Therefore, strategies are being developed that allow the in vivo amplification or isolation, in vitro expansion and genetic manipulation of beneficial T cells for adoptive cell therapies or for the tolerization, or elimination of pathogenic T cells. The major goal is to make use of the exquisite antigen specificity of T cells to develop targeted strategies and to develop techniques that allow for the identification and depletion or enrichment of very often rare antigen-specific naïve as well as effector and memory T cells. Such techniques are very useful for immune monitoring of T cell responses in diagnostics and vaccination and for the development of T cell-based assays for the replacement of animal testing in immunotoxicology to identify contact allergens and drugs that cause adverse reactions.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

ACD:

Allergic contact dermatitis

APC:

Antigen-presenting cell

CHS:

Contact hypersensitivity

CMV:

Cytomegalovirus

CSA:

Cytokine secretion assay

DNBS:

2,4-Dinitrobenzene sulfonic acid

hTCPA:

human T cell priming assay

LLNA:

Local lymph node assay

MHC:

Major histocompatibility complex

PBMC:

Peripheral blood mononuclear cell

TCR:

T cell receptor

TNBS:

2,4,6-Trinitrobenzene sulfonic acid

References

  • Adler S, Basketter D, Creton S, Pelkonen O, van Benthem J, Zuang V, Andersen KE, Angers-Loustau A, Aptula A, Bal-Price A, Benfenati E, Bernauer U, Bessems J, Bois FY, Boobis A, Brandon E, Bremer S, Broschard T, Casati S, Coecke S, Corvi R, Cronin M, Daston G, Dekant W, Felter S, Grignard E, Gundert-Remy U, Heinonen T, Kimber I, Kleinjans J, Komulainen H, Kreiling R, Kreysa J, Leite SB, Loizou G, Maxwell G, Mazzatorta P, Munn S, Pfuhler S, Phrakonkham P, Piersma A, Poth A, Prieto P, Repetto G, Rogiers V, Schoeters G, Schwarz M, Serafimova R, Tahti H, Testai E, van Delft J, van Loveren H, Vinken M, Worth A, Zaldivar JM (2011) Alternative (non-animal) methods for cosmetics testing: current status and future prospects-2010. Arch Toxicol 85:367–485

    Article  CAS  PubMed  Google Scholar 

  • Alanio C, Lemaitre F, Law HK, Hasan M, Albert ML (2010) Enumeration of human antigen-specific naive CD8+ T cells reveals conserved precursor frequencies. Blood 115:3718–3725

    Article  CAS  PubMed  Google Scholar 

  • Allam JP, Novak N (2011) Local immunological mechanisms of sublingual immunotherapy. Curr Opin Allergy Clin Immunol 11:571–578

    Article  CAS  PubMed  Google Scholar 

  • Andersen RS, Kvistborg P, Frosig TM, Pedersen NW, Lyngaa R, Bakker AH, Shu CJ, Straten P, Schumacher TN, Hadrup SR (2012) Parallel detection of antigen-specific T cell responses by combinatorial encoding of MHC multimers. Nat Protoc 7:891–902

    Article  CAS  PubMed  Google Scholar 

  • Atarashi Y, Kanaya H, Whieside TL (2000) A modified JAM assay detects apoptosis induced in activated lymphocytes by FasL+ human adherent tumor cells. J Immunol Methods 233:179–183

    Article  CAS  PubMed  Google Scholar 

  • Bacher P, Scheffold A (2013) Flow-cytometric analysis of rare antigen-specific T cells. Cytometry A 83:692–701

    PubMed  Google Scholar 

  • Bacher P, Schink C, Teutschbein J, Kniemeyer O, Assenmacher M, Brakhage AA, Scheffold A (2013) Antigen-reactive T cell enrichment for direct, high-resolution analysis of the human naive and memory Th cell repertoire. J Immunol 190:3967–3976

    Article  CAS  PubMed  Google Scholar 

  • Barbaud A (2009) Skin testing in delayed reactions to drugs. Immunol Allergy Clin North Am 29:517–535

    Article  PubMed  Google Scholar 

  • Battaglia M, Roncarolo MG (2011) Immune intervention with T regulatory cells: past lessons and future perspectives for type 1 diabetes. Semin Immunol 23:182–194

    Article  CAS  PubMed  Google Scholar 

  • Betts MR, Brenchley JM, Price DA, De Rosa SC, Douek DC, Roederer M, Koup RA (2003) Sensitive and viable identification of antigen-specific CD8+ T cells by a flow cytometric assay for degranulation. J Immunol Methods 281:65–78

    Article  CAS  PubMed  Google Scholar 

  • Bohm C, Hanski ML, Gratchev A, Mann B, Moyer MP, Riecken EO, Hanski C (1998) A modification of the JAM test is necessary for a correct determination of apoptosis induced by FasL+ adherent tumor cells. J Immunol Methods 217:71–78

    Article  CAS  PubMed  Google Scholar 

  • Bour-Jordan H, Esensten JH, Martinez-Llordella M, Penaranda C, Stumpf M, Bluestone JA (2011) Intrinsic and extrinsic control of peripheral T-cell tolerance by costimulatory molecules of the CD28/ B7 family. Immunol Rev 241:180–205

    Article  CAS  PubMed  Google Scholar 

  • Boyle DS, Hawkins KR, Steele MS, Singhal M, Cheng X (2012) Emerging technologies for point-of-care CD4 T-lymphocyte counting. Trends Biotechnol 30:45–54

    Article  CAS  PubMed  Google Scholar 

  • Britten CM, Meyer RG, Graf C, Huber C, Wolfel T (2005) Identification of T cell epitopes by the use of rapidly generated mRNA fragments. J Immunol Methods 299:165–175

    Article  CAS  PubMed  Google Scholar 

  • Brosterhus H, Brings S, Leyendeckers H, Manz RA, Miltenyi S, Radbruch A, Assenmacher M, Schmitz J (1999) Enrichment and detection of live antigen-specific CD4(+) and CD8(+) T cells based on cytokine secretion. Eur J Immunol 29:4053–4059

    Article  CAS  PubMed  Google Scholar 

  • Brunner KT, Mauel J, Cerottini JC, Chapuis B (1968) Quantitative assay of the lytic action of immune lymphoid cells on 51-Cr-labelled allogeneic target cells in vitro; inhibition by isoantibody and by drugs. Immunology 14:181–196

    CAS  PubMed  Google Scholar 

  • Byrne WL, Mills KH, Lederer JA, O’Sullivan GC (2011) Targeting regulatory T cells in cancer. Cancer Res 71:6915–6920

    Article  CAS  PubMed  Google Scholar 

  • Campbell JD, Buchmann P, Kesting S, Cunningham CR, Coffman RL, Hessel EM (2010) Allergen-specific T cell responses to immunotherapy monitored by CD154 and intracellular cytokine expression. Clin Exp Allergy 40:1025–1035

    Article  CAS  PubMed  Google Scholar 

  • Campbell JD, Foerster A, Lasmanowicz V, Niemoller M, Scheffold A, Fahrendorff M, Rauser G, Assenmacher M, Richter A (2011) Rapid detection, enrichment and propagation of specific T cell subsets based on cytokine secretion. Clin Exp Immunol 163:1–10

    Article  CAS  PubMed  Google Scholar 

  • Cheadle EJ, Sheard V, Hombach AA, Chmielewski M, Riet T, Berrevoets C, Schooten E, Lamers C, Abken H, Debets R, Gilham DE (2012) Chimeric antigen receptors for T-cell based therapy. Methods Mol Biol 907:645–666

    CAS  PubMed  Google Scholar 

  • Coppieters K, Amirian N, von Herrath M (2012) Intravital imaging of CTLs killing islet cells in diabetic mice. J Clin Invest 122:119–131

    Article  CAS  PubMed  Google Scholar 

  • Crawford F, Jordan KR, Stadinski B, Wang Y, Huseby E, Marrack P, Slansky JE, Kappler JW (2006) Use of baculovirus MHC/peptide display libraries to characterize T-cell receptor ligands. Immunol Rev 210:156–170

    Article  CAS  PubMed  Google Scholar 

  • Daniel C, von Boehmer H (2011) Extrathymic generation of regulatory T cells–chances and challenges for prevention of autoimmune disease. Adv Immunol 112:177–213

    Article  PubMed  Google Scholar 

  • Davenport MP, Ribeiro RM, Zhang L, Wilson DP, Perelson AS (2007) Understanding the mechanisms and limitations of immune control of HIV. Immunol Rev 216:164–175

    PubMed  Google Scholar 

  • Davis MM, Altman JD, Newell EW (2011) Interrogating the repertoire: broadening the scope of peptide-MHC multimer analysis. Nat Rev Immunol 11:551–558

    Article  CAS  PubMed  Google Scholar 

  • Dickel H, Altmeyer P, Brasch J (2011) “New” techniques for more sensitive patch testing? J Dtsch Dermatol Ges 9:889–896

    PubMed  Google Scholar 

  • Dietz L, Esser PR, Schmucker SS, Goette I, Richter A, Schnolzer M, Martin SF, Thierse HJ (2010) Tracking human contact allergens: from mass spectrometric identification of peptide-bound reactive small chemicals to chemical-specific naive human T-cell priming. Toxicol Sci 117:336–347

    Article  CAS  PubMed  Google Scholar 

  • Drake CG (2012) Combination immunotherapy approaches. Ann Oncol 23(Suppl 8):viii41–viii46

    Article  PubMed  Google Scholar 

  • Faulkner L, Martinsson K, Santoyo-Castelazo A, Cederbrant K, Schuppe-Koistinen I, Powell H, Tugwood J, Naisbitt DJ, Park BK (2012) The development of in vitro culture methods to characterize primary T-cell responses to drugs. Toxicol Sci 127:150–158

    Article  CAS  PubMed  Google Scholar 

  • Frentsch M, Arbach O, Kirchhoff D, Moewes B, Worm M, Rothe M, Scheffold A, Thiel A (2005) Direct access to CD4+ T cells specific for defined antigens according to CD154 expression. Nat Med 11:1118–1124

    Article  CAS  PubMed  Google Scholar 

  • Geiger R, Duhen T, Lanzavecchia A, Sallusto F (2009) Human naive and memory CD4+ T cell repertoires specific for naturally processed antigens analyzed using libraries of amplified T cells. J Exp Med 206:1525–1534

    Article  CAS  PubMed  Google Scholar 

  • Getts DR, Shankar S, Chastain EM, Martin A, Getts MT, Wood K, Miller SD (2011) Current landscape for T-cell targeting in autoimmunity and transplantation. Immunotherapy 3:853–870

    Article  CAS  PubMed  Google Scholar 

  • Gilchuk P, Spencer CT, Conant SB, Hill T, Gray JJ, Niu X, Zheng M, Erickson JJ, Boyd KL, McAfee KJ, Oseroff C, Hadrup SR, Bennink JR, Hildebrand W, Edwards KM, Crowe JE Jr, Williams JV, Buus S, Sette A, Schumacher TN, Link AJ, Joyce S (2013) Discovering naturally processed antigenic determinants that confer protective T cell immunity. J Clin Invest 123:1976–1987

    Article  CAS  PubMed  Google Scholar 

  • Gilham DE, Debets R, Pule M, Hawkins RE, Abken H (2012) CAR-T cells and solid tumors: tuning T cells to challenge an inveterate foe. Trends Mol Med 18:377–384

    Article  CAS  PubMed  Google Scholar 

  • Godoy-Ramirez K, Makitalo B, Thorstensson R, Sandstrom E, Biberfeld G, Gaines H (2005) A novel assay for assessment of HIV-specific cytotoxicity by multiparameter flow cytometry. Cytometry A 68:71–80

    PubMed  Google Scholar 

  • Greten TF, Schneck JP (2002) Development and use of multimeric major histocompatibility complex molecules. Clin Diagn Lab Immunol 9:216–220

    CAS  PubMed  Google Scholar 

  • Haanen JB, van Oijen MG, Tirion F, Oomen LC, Kruisbeek AM, Vyth-Dreese FA, Schumacher TN (2000) In situ detection of virus- and tumor-specific T-cell immunity. Nat Med 6:1056–1060

    Article  CAS  PubMed  Google Scholar 

  • Hadrup SR, Bakker AH, Shu CJ, Andersen RS, van Veluw J, Hombrink P, Castermans E, Thor Straten P, Blank C, Haanen JB, Heemskerk MH, Schumacher TN (2009) Parallel detection of antigen-specific T-cell responses by multidimensional encoding of MHC multimers. Nat Methods 6:520–526

    Article  CAS  PubMed  Google Scholar 

  • Hillen N, Stevanovic S (2006) Contribution of mass spectrometry-based proteomics to immunology. Expert Rev Proteomics 3:653–664

    Article  CAS  PubMed  Google Scholar 

  • Holgate ST (2012) Innate and adaptive immune responses in asthma. Nat Med 18:673–683

    Article  CAS  PubMed  Google Scholar 

  • Hong JJ, Reynolds MR, Mattila TL, Hage A, Watkins DI, Miller CJ, Skinner PJ (2009) Localized populations of CD8 MHC class I tetramer SIV-specific T cells in lymphoid follicles and genital epithelium. PLoS One 4:e4131

    Article  PubMed  Google Scholar 

  • Hoves S, Krause SW, Scholmerich J, Fleck M (2003) The JAM-assay: optimized conditions to determine death-receptor-mediated apoptosis. Methods 31:127–134

    Article  CAS  PubMed  Google Scholar 

  • Jahn-Schmid B, Pickl WF, Bohle B (2011) Interaction of allergens, major histocompatibility complex molecules, and T cell receptors: a ‘menage a trois’ that opens new avenues for therapeutic intervention in type I allergy. Int Arch Allergy Immunol 156:27–42

    Article  CAS  PubMed  Google Scholar 

  • Jenkins MK, Moon JJ (2012) The role of naive T cell precursor frequency and recruitment in dictating immune response magnitude. J Immunol 188:4135–4140

    Article  CAS  PubMed  Google Scholar 

  • Jorritsma A, Schotte R, Coccoris M, de Witte MA, Schumacher TN (2011) Prospects and limitations of T cell receptor gene therapy. Curr Gene Ther 11:276–287

    Article  CAS  PubMed  Google Scholar 

  • Jowsey IR, Basketter DA, Westmoreland C, Kimber I (2006) A future approach to measuring relative skin sensitising potency: a proposal. J Appl Toxicol 26:341–350

    Article  CAS  PubMed  Google Scholar 

  • Kimber I, Maxwell G, Gilmour N, Dearman RJ, Friedmann PS, Martin SF (2012) Allergic contact dermatitis: a commentary on the relationship between T lymphocytes and skin sensitising potency. Toxicology 291:18–24

    Article  CAS  PubMed  Google Scholar 

  • Lan Q, Fan H, Quesniaux V, Ryffel B, Liu Z, Zheng SG (2012) Induced Foxp3(+) regulatory T cells: a potential new weapon to treat autoimmune and inflammatory diseases? J Mol Cell Biol 4:22–28

    Article  CAS  PubMed  Google Scholar 

  • Lash GE, Pinto LA (2010) Multiplex cytokine analysis technologies. Expert Rev Vaccines 9:1231–1237

    Article  CAS  PubMed  Google Scholar 

  • Lee S, Margolin K (2012) Tumor-infiltrating lymphocytes in melanoma. Curr Oncol Rep 14:468–474

    Article  CAS  PubMed  Google Scholar 

  • Lehmann PV, Zhang W (2012) Unique strengths of ELISPOT for T cell diagnostics. Methods Mol Biol 792:3–23

    Article  CAS  PubMed  Google Scholar 

  • Linnemann C, Schumacher TN, Bendle GM (2011) T-cell receptor gene therapy: critical parameters for clinical success. J Invest Dermatol 131:1806–1816

    Article  CAS  PubMed  Google Scholar 

  • Lizee G, Overwijk WW, Radvanyi L, Gao J, Sharma P, Hwu P (2013) Harnessing the power of the immune system to target cancer. Annu Rev Med 64:71–90

    Article  CAS  PubMed  Google Scholar 

  • Lyons AB (1999) Divided we stand: tracking cell proliferation with carboxyfluorescein diacetate succinimidyl ester. Immunol Cell Biol 77:509–515

    Article  CAS  PubMed  Google Scholar 

  • Lyons AB (2000) Analysing cell division in vivo and in vitro using flow cytometric measurement of CFSE dye dilution. J Immunol Methods 243:147–154

    Article  CAS  PubMed  Google Scholar 

  • Maecker HT, Lindstrom TM, Robinson WH, Utz PJ, Hale M, Boyd SD, Shen-Orr SS, Fathman CG (2012) New tools for classification and monitoring of autoimmune diseases. Nat Rev Rheumatol 8:317–328

    Article  CAS  PubMed  Google Scholar 

  • Maggi E, Vultaggio A, Matucci A (2012) T-cell responses during allergen-specific immunotherapy. Curr Opin Allergy Clin Immunol 12:1–6

    Article  CAS  PubMed  Google Scholar 

  • Maher J, Wilkie S (2009) CAR mechanics: driving T cells into the MUC of cancer. Cancer Res 69:4559–4562

    Article  CAS  PubMed  Google Scholar 

  • Makedonas G, Betts MR (2011) Living in a house of cards: re-evaluating CD8+ T-cell immune correlates against HIV. Immunol Rev 239:109–124

    Article  CAS  PubMed  Google Scholar 

  • Marcusson-Stahl M, Cederbrant K (2003) A flow-cytometric NK-cytotoxicity assay adapted for use in rat repeated dose toxicity studies. Toxicology 193:269–279

    Article  CAS  PubMed  Google Scholar 

  • Martin SF (2004) T lymphocyte-mediated immune responses to chemical haptens and metal ions: implications for allergic and autoimmune disease. Int Arch Allergy Immunol 134:186–198

    Article  CAS  PubMed  Google Scholar 

  • Martin SF, Esser PR, Schmucker S, Dietz L, Naisbitt DJ, Park BK, Vocanson M, Nicolas JF, Keller M, Pichler WJ, Peiser M, Luch A, Wanner R, Maggi E, Cavani A, Rustemeyer T, Richter A, Thierse HJ, Sallusto F (2010) T-cell recognition of chemicals, protein allergens and drugs: towards the development of in vitro assays. Cell Mol Life Sci 67:4171–4184

    Article  CAS  PubMed  Google Scholar 

  • Matzinger P (1991) The JAM test. A simple assay for DNA fragmentation and cell death. J Immunol Methods 145:185–192

    Article  CAS  PubMed  Google Scholar 

  • McKinney DM, Southwood S, Hinz D, Oseroff C, Arlehamn CS, Schulten V, Taplitz R, Broide D, Hanekom WA, Scriba TJ, Wood R, Alam R, Peters B, Sidney J, Sette A (2013) A strategy to determine HLA class II restriction broadly covering the DR, DP, and DQ allelic variants most commonly expressed in the general population. Immunogenetics 65:357–370

    Article  CAS  PubMed  Google Scholar 

  • McMichael AJ, Borrow P, Tomaras GD, Goonetilleke N, Haynes BF (2010) The immune response during acute HIV-1 infection: clues for vaccine development. Nat Rev Immunol 10:11–23

    Article  CAS  PubMed  Google Scholar 

  • Moon JJ, Chu HH, Hataye J, Pagan AJ, Pepper M, McLachlan JB, Zell T, Jenkins MK (2009) Tracking epitope-specific T cells. Nat Protoc 4:565–581

    Article  CAS  PubMed  Google Scholar 

  • Nagorsen D, Scheibenbogen C, Thiel E, Keilholz U (2004) Immunological monitoring of cancer vaccine therapy. Expert Opin Biol Ther 4:1677–1684

    Article  CAS  PubMed  Google Scholar 

  • Nepom GT (2012) MHC class II tetramers. J Immunol 188:2477–2482

    Article  CAS  PubMed  Google Scholar 

  • Nyfeler B, Pichler WJ (1997) The lymphocyte transformation test for the diagnosis of drug allergy: sensitivity and specificity. Clin Exp Allergy 27:175–181

    Article  CAS  PubMed  Google Scholar 

  • Oelke M, Schneck JP (2010) Overview of a HLA-Ig based “Lego-like system” for T cell monitoring, modulation and expansion. Immunol Res 47:248–256

    Article  CAS  PubMed  Google Scholar 

  • Park TS, Rosenberg SA, Morgan RA (2011) Treating cancer with genetically engineered T cells. Trends Biotechnol 29:550–557

    Article  CAS  PubMed  Google Scholar 

  • Pichler WJ, Tilch J (2004) The lymphocyte transformation test in the diagnosis of drug hypersensitivity. Allergy 59:809–820

    Article  CAS  PubMed  Google Scholar 

  • Pittet MJ, Speiser DE, Valmori D, Rimoldi D, Lienard D, Lejeune F, Cerottini JC, Romero P (2001) Ex vivo analysis of tumor antigen specific CD8+ T cell responses using MHC/peptide tetramers in cancer patients. Int Immunopharmacol 1:1235–1247

    Article  CAS  PubMed  Google Scholar 

  • Quezada SA, Peggs KS, Simpson TR, Allison JP (2011) Shifting the equilibrium in cancer immunoediting: from tumor tolerance to eradication. Immunol Rev 241:104–118

    Article  CAS  PubMed  Google Scholar 

  • Rammensee H, Bachmann J, Emmerich NP, Bachor OA, Stevanovic S (1999) SYFPEITHI: database for MHC ligands and peptide motifs. Immunogenetics 50:213–219

    Article  CAS  PubMed  Google Scholar 

  • Ramos CA, Dotti G (2011) Chimeric antigen receptor (CAR)-engineered lymphocytes for cancer therapy. Expert Opin Biol Ther 11:855–873

    Article  CAS  PubMed  Google Scholar 

  • Restifo NP, Dudley ME, Rosenberg SA (2012) Adoptive immunotherapy for cancer: harnessing the T cell response. Nat Rev Immunol 12:269–281

    Article  CAS  PubMed  Google Scholar 

  • Richter A, Schmucker SS, Esser PR, Traska V, Weber V, Dietz L, Thierse HJ, Pennino D, Cavani A, Martin SF (2013) Human T cell priming assay (hTCPA) for the identification of contact allergens based on naive T cells and DC–IFN-gamma and TNF-alpha readout. Toxicol In Vitro 27:1180–1185

    Article  CAS  PubMed  Google Scholar 

  • Rosenberg SA, Dudley ME (2009) Adoptive cell therapy for the treatment of patients with metastatic melanoma. Curr Opin Immunol 21:233–240

    Article  CAS  PubMed  Google Scholar 

  • Rubio V, Stuge TB, Singh N, Betts MR, Weber JS, Roederer M, Lee PP (2003) Ex vivo identification, isolation and analysis of tumor-cytolytic T cells. Nat Med 9:1377–1382

    Article  CAS  PubMed  Google Scholar 

  • Salimi N, Fleri W, Peters B, Sette A (2012) The immune epitope database: a historical retrospective of the first decade. Immunology 137:117–123

    Article  CAS  PubMed  Google Scholar 

  • Sallusto F, Impellizzieri D, Basso C, Laroni A, Uccelli A, Lanzavecchia A, Engelhardt B (2012) T-cell trafficking in the central nervous system. Immunol Rev 248:216–227

    Article  PubMed  Google Scholar 

  • Schuler MM, Donnes P, Nastke MD, Kohlbacher O, Rammensee HG, Stevanovic S (2005) SNEP: SNP-derived epitope prediction program for minor H antigens. Immunogenetics 57:816–820

    Article  CAS  PubMed  Google Scholar 

  • Schulten V, Oseroff C, Alam R, Broide D, Vijayanand P, Peters B, Sette A (2013) The identification of potentially pathogenic and therapeutic epitopes from common human allergens. Ann Allergy Asthma Immunol 110:7–10

    Article  CAS  PubMed  Google Scholar 

  • Shirasu N, Kuroki M (2012) Functional design of chimeric T-cell antigen receptors for adoptive immunotherapy of cancer: architecture and outcomes. Anticancer Res 32:2377–2383

    CAS  PubMed  Google Scholar 

  • Siewert K, Malotka J, Kawakami N, Wekerle H, Hohlfeld R, Dornmair K (2012) Unbiased identification of target antigens of CD8+ T cells with combinatorial libraries coding for short peptides. Nat Med 18:824–828

    Article  CAS  PubMed  Google Scholar 

  • Sims S, Willberg C, Klenerman P (2010) MHC-peptide tetramers for the analysis of antigen-specific T cells. Expert Rev Vaccines 9:765–774

    Article  CAS  PubMed  Google Scholar 

  • Skinner PJ, Haase AT (2002) In situ tetramer staining. J Immunol Methods 268:29–34

    Article  CAS  PubMed  Google Scholar 

  • Skinner PJ, Haase AT (2005) In situ staining using MHC class I tetramers. Curr Protoc Immunol Chap. 17:Unit 17 14.

    Google Scholar 

  • Tang Q, Bluestone JA, Kang SM (2012) CD4(+)Foxp3(+) regulatory T cell therapy in transplantation. J Mol Cell Biol 4:11–21

    Article  CAS  PubMed  Google Scholar 

  • Thiel A, Scheffold A, Radbruch A (2004) Antigen-specific cytometry–new tools arrived! Clin Immunol 111:155–161

    Article  CAS  PubMed  Google Scholar 

  • Toebes M, Coccoris M, Bins A, Rodenko B, Gomez R, Nieuwkoop NJ, van de Kasteele W, Rimmelzwaan GF, Haanen JB, Ovaa H, Schumacher TN (2006) Design and use of conditional MHC class I ligands. Nat Med 12:246–251

    Article  CAS  PubMed  Google Scholar 

  • Toebes M, Rodenko B, Ovaa H, Schumacher TN (2009) Generation of peptide MHC class I monomers and multimers through ligand exchange. Curr Protoc Immunol Chap. 18:Unit 18 16.

    Google Scholar 

  • Turtle CJ, Hudecek M, Jensen MC, Riddell SR (2012) Engineered T cells for anti-cancer therapy. Curr Opin Immunol 24:633–639

    Article  CAS  PubMed  Google Scholar 

  • Vaughan K, Kim Y, Sette A (2012) A comparison of epitope repertoires associated with myasthenia gravis in humans and nonhuman hosts. Autoimmune Dis 2012:403915

    PubMed  Google Scholar 

  • Vocanson M, Cluzel-Tailhardat M, Poyet G, Valeyrie M, Chavagnac C, Levarlet B, Courtellemont P, Rozieres A, Hennino A, Nicolas JF (2008) Depletion of human peripheral blood lymphocytes in CD25+ cells allows for the sensitive in vitro screening of contact allergens. J Invest Dermatol 128:2119–2122

    Article  CAS  PubMed  Google Scholar 

  • Vyth-Dreese FA, Kim YH, Dellemijn TA, Schrama E, Haanen JB, Spierings E, Goulmy E (2006) In situ visualization of antigen-specific T cells in cryopreserved human tissues. J Immunol Methods 310:78–85

    Article  CAS  PubMed  Google Scholar 

  • Wang A, Chandran S, Shah SA, Chiu Y, Paria BC, Aghamolla T, Alvarez-Downing MM, Lee CC, Singh S, Li T, Dudley ME, Restifo NP, Rosenberg SA, Kammula US (2012) The stoichiometric production of IL-2 and IFN-gamma mRNA defines memory T cells that can self-renew after adoptive transfer in humans. Sci Transl Med 4:149ra120

    Article  PubMed  Google Scholar 

  • Wolk B, Trautwein C, Buchele B, Kersting N, Blum HE, Rammensee HG, Cerny A, Stevanovic S, Moradpour D, Brass V (2012) Identification of naturally processed hepatitis C virus-derived major histocompatibility complex class I ligands. PLoS One 7:e29286

    Article  PubMed  Google Scholar 

  • Wu RC, Liu S, Chacon JA, Wu S, Li Y, Sukhumalchandra P, Murray JL, Molldrem JJ, Hwu P, Pircher H, Lizee G, Radvanyi LG (2012) Detection and characterization of a novel subset of CD8(+)CD57(+) T cells in metastatic melanoma with an incompletely differentiated phenotype. Clin Cancer Res 18:2465–2477

    Article  CAS  PubMed  Google Scholar 

  • Yin L, Crawford F, Marrack P, Kappler JW, Dai S (2012) T-cell receptor (TCR) interaction with peptides that mimic nickel offers insight into nickel contact allergy. Proc Natl Acad Sci U S A 109:18517–18522

    Article  CAS  PubMed  Google Scholar 

  • Zawodniak A, Lochmatter P, Yerly D, Kawabata T, Lerch M, Yawalkar N, Pichler WJ (2010) In vitro detection of cytotoxic T and NK cells in peripheral blood of patients with various drug-induced skin diseases. Allergy 65:376–384

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Stefan F. Martin or Anne Richter .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Basel

About this chapter

Cite this chapter

Martin, S.F., Schmucker, S.S., Richter, A. (2014). Tools and Methods for Identification and Analysis of Rare Antigen-Specific T Lymphocytes. In: Martin, S. (eds) T Lymphocytes as Tools in Diagnostics and Immunotoxicology. Experientia Supplementum, vol 104. Springer, Basel. https://doi.org/10.1007/978-3-0348-0726-5_6

Download citation

Publish with us

Policies and ethics