Vagaries of the ELISpot assay: SPECIFIC detection of antigen responsive cells requires purified CD8+ T cells and MHC class I expressing antigen presenting cell lines

Clinical Immunology

Volumn 157, Issue 2, 2015, Pages 216-225

  Fuchs, Yannick F ^a,b,c   Jainta, Gregor W ^a   Kühn, Denise ^a   Wilhelm, Carmen ^a   Weigelt, Marc ^a   Karasinsky, Anne ^a   Upadhyaya, Bhaskar ^a   Ziegler, Anette G ^c,d   Bonifacio, Ezio ^a,b,d  

^a CENTER FOR REGENERATIVE THERAPIES DRESDEN   (Germany)

^b DRESDEN UNIVERSITY OF TECHNOLOGY   (Germany)

^c Forschergruppe Diabetes eV   (Germany)

^d TECHNICAL UNIVERSITY OF MUNICH   (Germany)

Author keywords

Autoantigen; CD8+ T cells; Diabetes; ELISpot; MHC class I

Indexed keywords

GAMMA INTERFERON; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 1; PREPROINSULIN; HLA A2 ANTIGEN; HLA ANTIGEN CLASS 1; HLA-A*02:01 ANTIGEN;

ADOLESCENT; ADULT; ANIMAL CELL; ANIMAL EXPERIMENT; ANTIGEN PRESENTATION; ANTIGEN PRESENTING CELL; ARTICLE; CD8+ T LYMPHOCYTE; CELLULAR IMMUNITY; CHILD; CONTROLLED STUDY; ENZYME LINKED IMMUNOSPOT ASSAY; FEMALE; FLUORESCENCE ACTIVATED CELL SORTING; HUMAN; HUMAN CELL; INTERFERON PRODUCTION; INTRACELLULAR SPACE; K562 CELL LINE; LIMIT OF DETECTION; LYMPHOCYTE ACTIVATION; MALE; MOUSE; NONHUMAN; NORMAL HUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; QUANTITATIVE ANALYSIS; ANIMAL; CASE CONTROL STUDY; IMMUNOLOGY; INSULIN DEPENDENT DIABETES MELLITUS; NONOBESE DIABETIC MOUSE; PROCEDURES; YOUNG ADULT;

ADOLESCENT; ANIMALS; ANTIGEN-PRESENTING CELLS; CASE-CONTROL STUDIES; CD8-POSITIVE T-LYMPHOCYTES; CHILD; DIABETES MELLITUS, TYPE 1; ENZYME-LINKED IMMUNOSPOT ASSAY; FEMALE; HISTOCOMPATIBILITY ANTIGENS CLASS I; HLA-A2 ANTIGEN; HUMANS; INTERFERON-GAMMA; K562 CELLS; MALE; MICE; MICE, INBRED NOD; YOUNG ADULT;

EID: 84924529824     PISSN: 15216616     EISSN: 15217035     Source Type: Journal    
DOI: 10.1016/j.clim.2015.02.012     Document Type: Article

References (38)

1. Arif S., Tree T.I., Astill T.P., Tremble J.M., Bishop A.J., Dayan C.M., Roep B.O., Peakman M. Autoreactive T cell responses show proinflammatory polarization in diabetes but a regulatory phenotype in health. J. Clin. Invest. 2004, 113:451-463.
2. Olsson T., Zhi W.W., Hojeberg B., Kostulas V., Jiang Y.P., Anderson G., Ekre H.P., Link H. Autoreactive T lymphocytes in multiple sclerosis determined by antigen-induced secretion of interferon-gamma. J. Clin. Invest. 1990, 86:981-985.
3. Lechner F., Wong D.K., Dunbar P.R., Chapman R., Chung R.T., Dohrenwend P., Robbins G., Phillips R., Klenerman P., Walker B.D. Analysis of successful immune responses in persons infected with hepatitis C virus. J. Exp. Med. 2000, 191:1499-1512.
4. McElrath M.J., De Rosa S.C., Moodie Z., Dubey S., Kierstead L., Janes H., Defawe O.D., Carter D.K., Hural J., Akondy R., Buchbinder S.P., Robertson M.N., Mehrotra D.V., Self S.G., Corey L., Shiver J.W., Casimiro D.R. HIV-1 vaccine-induced immunity in the test-of-concept Step Study: a case-cohort analysis. Lancet 2008, 372:1894-1905.
5. Soysal A., Millington K.A., Bakir M., Dosanjh D., Aslan Y., Deeks J.J., Efe S., Staveley I., Ewer K., Lalvani A. Effect of BCG vaccination on risk of Mycobacterium tuberculosis infection in children with household tuberculosis contact: a prospective community-based study. Lancet 2005, 366:1443-1451.
6. Zanone M.M., Favaro E., Quadri R., Miceli I., Giaretta F., Romagnoli R., David E., Perin P.C., Salizzoni M., Camussi G. Association of cytomegalovirus infections with recurrence of humoral and cellular autoimmunity to islet autoantigens and of type 1 diabetes in a pancreas transplanted patient. Transpl. Int. 2010, 23:333-337.
7. Martinuzzi E., Novelli G., Scotto M., Blancou P., Bach J.M., Chaillous L., Bruno G., Chatenoud L., van Endert P., Mallone R. The frequency and immunodominance of islet-specific CD8+ T-cell responses change after type 1 diabetes diagnosis and treatment. Diabetes 2008, 57:1312-1320.
8. Czerkinsky C., Andersson G., Ekre H.P., Nilsson L.A., Klareskog L., Ouchterlony O. Reverse ELISPOT assay for clonal analysis of cytokine production. I. Enumeration of gamma-interferon-secreting cells. J. Immunol. Methods 1988, 110:29-36.
9. Kabilan L., Andersson G., Lolli F., Ekre H.P., Olsson T., Troye-Blomberg M. Detection of intracellular expression and secretion of interferon-gamma at the single-cell level after activation of human T cells with tetanus toxoid in vitro. Eur. J. Immunol. 1990, 20:1085-1089.
10. Mallone R., Martinuzzi E., Blancou P., Novelli G., Afonso G., Dolz M., Bruno G., Chaillous L., Chatenoud L., Bach J.M., van Endert P. CD8+ T-cell responses identify beta-cell autoimmunity in human type 1 diabetes. Diabetes 2007, 56:613-621.
11. Blancou P., Mallone R., Martinuzzi E., Severe S., Pogu S., Novelli G., Bruno G., Charbonnel B., Dolz M., Chaillous L., van Endert P., Bach J.M. Immunization of HLA class I transgenic mice identifies autoantigenic epitopes eliciting dominant responses in type 1 diabetes patients. J. Immunol. 2007, 178:7458-7466.
12. Skowera A., Ellis R.J., Varela-Calvino R., Arif S., Huang G.C., Van-Krinks C., Zaremba A., Rackham C., Allen J.S., Tree T.I., Zhao M., Dayan C.M., Sewell A.K., Unger W.W., Drijfhout J.W., Ossendorp F., Roep B.O., Peakman M. CTLs are targeted to kill beta cells in patients with type 1 diabetes through recognition of a glucose-regulated preproinsulin epitope. J. Clin. Invest. 2008, 118:3390-3402.
13. Schirle M., Weinschenk T., Stevanovic S. Combining computer algorithms with experimental approaches permits the rapid and accurate identification of T cell epitopes from defined antigens. J. Immunol. Methods 2001, 257:1-16.
14. Rotzschke O., Falk K., Deres K., Schild H., Norda M., Metzger J., Jung G., Rammensee H.G. Isolation and analysis of naturally processed viral peptides as recognized by cytotoxic T cells. Nature 1990, 348:252-254.
15. Rammensee H.G., Falk K., Rotzschke O. Peptides naturally presented by MHC class I molecules. Annu. Rev. Immunol. 1993, 11:213-244.
16. Hammer J., Takacs B., Sinigaglia F. Identification of a motif for HLA-DR1 binding peptides using M13 display libraries. J. Exp. Med. 1992, 176:1007-1013.
17. Rammensee H.G., Friede T., Stevanoviic S. MHC ligands and peptide motifs: first listing. Immunogenetics 1995, 41:178-228.
18. Southwood S., Sidney J., Kondo A., del Guercio M.F., Appella E., Hoffman S., Kubo R.T., Chesnut R.W., Grey H.M., Sette A. Several common HLA-DR types share largely overlapping peptide binding repertoires. J. Immunol. 1998, 160:3363-3373.
19. Vogt A.B., Kropshofer H., Kalbacher H., Kalbus M., Rammensee H.G., Coligan J.E., Martin R. Ligand motifs of HLA-DRB5*0101 and DRB1*1501 molecules delineated from self-peptides. J. Immunol. 1994, 153:1665-1673.
20. Wucherpfennig K.W., Sette A., Southwood S., Oseroff C., Matsui M., Strominger J.L., Hafler D.A. Structural requirements for binding of an immunodominant myelin basic protein peptide to DR2 isotypes and for its recognition by human T cell clones. J. Exp. Med. 1994, 179:279-290.
21. Hemmer B., Kondo T., Gran B., Pinilla C., Cortese I., Pascal J., Tzou A., McFarland H.F., Houghten R., Martin R. Minimal peptide length requirements for CD4(+) T cell clones-implications for molecular mimicry and T cell survival. Int. Immunol. 2000, 12:375-383.
22. Reddehase M.J., Rothbard J.B., Koszinowski U.H. A pentapeptide as minimal antigenic determinant for MHC class I-restricted T lymphocytes. Nature 1989, 337:651-653.
23. Hansen S.G., Sacha J.B., Hughes C.M., Ford J.C., Burwitz B.J., Scholz I., Gilbride R.M., Lewis M.S., Gilliam A.N., Ventura A.B., Malouli D., Xu G., Richards R., Whizin N., Reed J.S., Hammond K.B., Fischer M., Turner J.M., Legasse A.W., Axthelm M.K., Edlefsen P.T., Nelson J.A., Lifson J.D., Fruh K., Picker L.J. Cytomegalovirus vectors violate CD8+ T cell epitope recognition paradigms. Science 2013, 340:1237874.
24. Wooldridge L., Ekeruche-Makinde J., van den Berg H.A., Skowera A., Miles J.J., Tan M.P., Dolton G., Clement M., Llewellyn-Lacey S., Price D.A., Peakman M., Sewell A.K. A single autoimmune T cell receptor recognizes more than a million different peptides. J. Biol. Chem. 2012, 287:1168-1177.
25. Fuchs Y.F., Adler K., Bonifacio E. Beta-cell autoimmunity. Methods Mol. Biol. 2012, 933:265-274.
26. Britten C.M., Meyer R.G., Kreer T., Drexler I., Wolfel T., Herr W. The use of HLA-A*0201-transfected K562 as standard antigen-presenting cells for CD8(+) T lymphocytes in IFN-gamma ELISPOT assays. J. Immunol. Methods 2002, 259:95-110.
27. Borg D.J., Weigelt M., Wilhelm C., Gerlach M., Bickle M., Speier S., Bonifacio E., Hommel A. Mesenchymal stromal cells improve transplanted islet survival and islet function in a syngeneic mouse model. Diabetologia 2014, 57:522-531.
28. Jarchum I., Takaki T., DiLorenzo T.P. Efficient culture of CD8(+) T cells from the islets of NOD mice and their use for the study of autoreactive specificities. J. Immunol. Methods 2008, 339:66-73.
29. Takaki T., Marron M.P., Mathews C.E., Guttmann S.T., Bottino R., Trucco M., DiLorenzo T.P., Serreze D.V. HLA-A*0201-restricted T cells from humanized NOD mice recognize autoantigens of potential clinical relevance to type 1 diabetes. J. Immunol. 2006, 176:3257-3265.
30. Wang C., Sanders C.M., Yang Q., Schroeder H.W., Wang E., Babrzadeh F., Gharizadeh B., Myers R.M., Hudson J.R., Davis R.W., Han J. High throughput sequencing reveals a complex pattern of dynamic interrelationships among human T cell subsets. Proc. Natl. Acad. Sci. U. S. A. 2010, 107:1518-1523.
31. Hammer J., Belunis C., Bolin D., Papadopoulos J., Walsky R., Higelin J., Danho W., Sinigaglia F., Nagy Z.A. High-affinity binding of short peptides to major histocompatibility complex class II molecules by anchor combinations. Proc. Natl. Acad. Sci. U. S. A. 1994, 91:4456-4460.
32. Wang M., Tang S.T., Stryhn A., Justesen S., Larsen M.V., Dziegiel M.H., Lewinsohn D.M., Buus S., Lund O., Claesson M.H. Identification of MHC class II restricted T-cell-mediated reactivity against MHC class I binding Mycobacterium tuberculosis peptides. Immunology 2011, 132:482-491.
33. Rammensee H.G. Chemistry of peptides associated with MHC class I and class II molecules. Curr. Opin. Immunol. 1995, 7:85-96.
34. Britten C.M., Meyer R.G., Frankenberg N., Huber C., Wolfel T. The use of clonal mRNA as an antigenic format for the detection of antigen-specific T lymphocytes in IFN-gamma ELISPOT assays. J. Immunol. Methods 2004, 287:125-136.
35. Enee E., Kratzer R., Arnoux J.B., Barilleau E., Hamel Y., Marchi C., Beltrand J., Michaud B., Chatenoud L., Robert J.J., van Endert P. ZnT8 is a major CD8+ T cell-recognized autoantigen in pediatric type 1 diabetes. Diabetes 2012, 61:1779-1784.
36. Ouyang Q., Standifer N.E., Qin H., Gottlieb P., Verchere C.B., Nepom G.T., Tan R., Panagiotopoulos C. Recognition of HLA class I-restricted beta-cell epitopes in type 1 diabetes. Diabetes 2006, 55:3068-3074.
37. Panagiotopoulos C., Qin H., Tan R., Verchere C.B. Identification of a beta-cell-specific HLA class I restricted epitope in type 1 diabetes. Diabetes 2003, 52:2647-2651.
38. Toma A., Haddouk S., Briand J.P., Camoin L., Gahery H., Connan F., Dubois-Laforgue D., Caillat-Zucman S., Guillet J.G., Carel J.C., Muller S., Choppin J., Boitard C. Recognition of a subregion of human proinsulin by class I-restricted T cells in type 1 diabetic patients. Proc. Natl. Acad. Sci. U. S. A. 2005, 102:10581-10586. (Figure Legends).