Misinitiation of intrathymic MART-1 transcription and biased TCR usage explain the high frequency of MART-1-specific T cells

European Journal of Immunology

Volumn 44, Issue 9, 2014, Pages 2811-2821

  Pinto, Sheena ^a   Sommermeyer, Daniel ^b,f   Michel, Chloé ^a   Wilde, Susanne ^c   Schendel, Dolores ^c   Uckert, Wolfgang ^b,d   Blankenstein, Thomas ^b,e   Kyewski, Bruno ^a  

^a GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

^b MAX DELBRÜCK CENTER FOR MOLECULAR MEDICINE   (Germany)

^c INSTITUTE OF EPIDEMIOLOGY   (Germany)

^d HUMBOLDT UNIVERSITY   (Germany)

^e CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^f Fred Hutchinson Cancer Research Center   (United States)

Author keywords

Central tolerance; Human medullary thymic epithelial cells; MART 1; Melanoma; Promiscuous gene expression

Indexed keywords

EPITOPE; HLA A2 ANTIGEN; LYMPHOCYTE ANTIGEN RECEPTOR; MELAN A; MLANA PROTEIN, HUMAN;

ARTICLE; CD8+ T LYMPHOCYTE; CELL LINE; CLINICAL TRIAL; CYTOLOGY; EPITHELIUM CELL; FEMALE; HUMAN; HUMAN MEDULLARY THYMIC EPITHELIAL CELLS; IMMUNOLOGICAL TOLERANCE; IMMUNOLOGY; MALE; MART-1; MELANOMA; PROMISCUOUS GENE EXPRESSION; THYMUS; TRANSCRIPTION INITIATION;

CENTRAL TOLERANCE; HUMAN MEDULLARY THYMIC EPITHELIAL CELLS; MART-1; MELANOMA; PROMISCUOUS GENE EXPRESSION;

CD8-POSITIVE T-LYMPHOCYTES; CELL LINE; EPITHELIAL CELLS; EPITOPES, T-LYMPHOCYTE; FEMALE; HLA-A2 ANTIGEN; HUMANS; MALE; MART-1 ANTIGEN; RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA; THYMUS GLAND; TRANSCRIPTION INITIATION, GENETIC;

EID: 84907830964     PISSN: 00142980     EISSN: 15214141     Source Type: Journal    
DOI: 10.1002/eji.201444499     Document Type: Article

References (41)

1. Coulie, P. G., Brichard, V., Van Pel, A., Wolfel, T., Schneider, J., Traversari, C., Mattei, S. et al., A new gene coding for a differentiation antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas. J. Exp. Med. 1994. 180: 35-42.
2. Kawakami, Y., Eliyahu, S., Delgado, C. H., Robbins, P. F., Rivoltini, L., Topalian, S. L., Miki, T. and Rosenberg, S. A., Cloning of the gene coding for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor. Proc. Natl. Acad. Sci. U S A 1994. 91: 3515-3519.
3. Zippelius, A., Pittet, M. J., Batard, P., Rufer, N., de Smedt, M., Guillaume, P., Ellefsen, K. et al., Thymic selection generates a large T cell pool recognizing a self-peptide in humans. J. Exp. Med. 2002. 195: 485-494.
4. Loftus, D. J., Castelli, C., Clay, T. M., Squarcina, P., Marincola, F. M., Nishimura, M. I., Parmiani, G. et al., Identification of epitope mimics recognized by CTL reactive to the melanoma/melanocyte-derived peptide MART-1(27-35). J. Exp. Med. 1996. 184: 647-657.
5. Schreiber, H., Cancer immunology. In Paul, W. E. (7th ed.) Fundamental Immunology. Wolters Kluwer Health/Lippincott Williams & Wilkins, Philadelphia 2013, pp 1200-1234.
6. Dutoit, V., Rubio-Godoy, V., Pittet, M. J., Zippelius, A., Dietrich, P. Y., Legal, F. A., Guillaume, P. et al., Degeneracy of antigen recognition as the molecular basis for the high frequency of naive A2/Melan-a peptide multimer(+) CD8(+) T cells in humans. J. Exp. Med. 2002. 196: 207-216.
7. Klein, L., Klein, T., Ruther, U. and Kyewski, B., CD4 T cell tolerance to human C-reactive protein, an inducible serum protein, is mediated by medullary thymic epithelium. J. Exp. Med. 1998. 188: 5-16.
8. Zehn, D. and Bevan, M. J., T cells with low avidity for a tissue-restricted antigen routinely evade central and peripheral tolerance and cause autoimmunity. Immunity 2006. 25: 261-270.
9. Trager, U., Sierro, S., Djordjevic, G., Bouzo, B., Khandwala, S., Meloni, A., Mortensen, M. et al., The immune response to melanoma is limited by thymic selection of self-antigens. PLoS One 2012. 7: e35005.
10. Gotter, J., Brors, B., Hergenhahn, M. and Kyewski, B., Medullary epithelial cells of the human thymus express a highly diverse selection of tissuespecific genes colocalized in chromosomal clusters. J. Exp. Med. 2004. 199: 155-166.
11. Takase, H., Yu, C. R., Mahdi, R. M., Douek, D. C., Dirusso, G. B., Midgley, F. M., Dogra, R. et al., Thymic expression of peripheral tissue antigens in humans: a remarkable variability among individuals. Int. Immunol. 2005. 17: 1131-1140.
12. Klein, L., Klugmann, M., Nave, K. A., Tuohy, V. K. and Kyewski, B., Shaping of the autoreactive T-cell repertoire by a splice variant of self protein expressed in thymic epithelial cells. Nat. Med. 2000. 6: 56- 61.
13. Villasenor, J., Besse, W., Benoist, C. and Mathis, D., Ectopic expression of peripheral-tissue antigens in the thymic epithelium: probabilistic, monoallelic, misinitiated. Proc. Natl. Acad. Sci. U S A 2008. 105: 15854- 15859.
14. Kyewski, B. and Klein, L., A central role for central tolerance. Annu. Rev. Immunol. 2006. 24: 571-606.
15. Wilde, S., Sommermeyer, D., Frankenberger, B., Schiemann, M., Milosevic, S., Spranger, S., Pohla, H. et al., Dendritic cells pulsed with RNA encoding allogeneic MHC and antigen induce T cells with superior antitumor activity and higher TCR functional avidity. Blood 2009. 114: 2131- 2139.
16. Trautmann, L., Labarriere, N., Jotereau, F., Karanikas, V., Gervois, N., Connerotte, T., Coulie, P. et al., Dominant TCR V alpha usage by virus and tumor-reactive T cells with wide affinity ranges for their specific antigens. Eur. J. Immunol. 2002. 32: 3181-3190.
17. Dietrich, P. Y., Le Gal, F. A., Dutoit, V., Pittet, M. J., Trautman, L., Zippelius, A., Cognet, I. et al., Prevalent role of TCR alpha-chain in the selection of the preimmune repertoire specific for a human tumor-associated self-antigen. J. Immunol. 2003. 170: 5103-5109.
18. Cole, D. K., Yuan, F., Rizkallah, P. J., Miles, J. J., Gostick, E., Price, D. A., Gao, G. F. et al., Germ line-governed recognition of a cancer epitope by an immunodominant human T-cell receptor. J. Biol. Chem. 2009. 284: 27281-27289.
19. Liang, X., Weigand, L. U., Schuster, I. G., Eppinger, E., van der Griendt, J. C., Schub, A., Leisegang, M. et al., A single TCR alpha-chain with dominant peptide recognition in the allorestricted HER2/neu-specific T cell repertoire. J. Immunol. 2010. 184: 1617-1629.
20. Li, L. P., Lampert, J. C., Chen, X., Leitao, C., Popovic, J., Muller, W. and Blankenstein, T., Transgenic mice with a diverse human T cell antigen receptor repertoire. Nat. Med. 2010. 16: 1029-1034.
21. Redmond, W. L. and Sherman, L. A., Peripheral tolerance of CD8 T lymphocytes. Immunity 2005. 22: 275-284.
22. Pittet, M. J., Zippelius, A., Valmori, D., Speiser, D. E., Cerottini, J. C. and Romero, P., Melan-A/MART-1-specific CD8 T cells: from thymus to tumor. Trends Immunol. 2002. 23: 325-328.
23. Morel, S., Levy, F., Burlet-Schiltz, O., Brasseur, F., Probst-Kepper, M., Peitrequin, A. L., Monsarrat, B. et al., Processing of some antigens by the standard proteasome but not by the immunoproteasome results in poor presentation by dendritic cells. Immunity 2000. 12: 107- 117.
24. Lv, H., Havari, E., Pinto, S., Gottumukkala, R. V., Cornivelli, L., Raddassi, K., Matsui, T. et al., Impaired thymic tolerance to alpha-myosin directs autoimmunity to the heart in mice and humans. J. Clin. Invest. 2011. 121: 1561-1573.
25. Pelechano, V., Wei, W. and Steinmetz, L. M., Extensive transcriptional heterogeneity revealed by isoform profiling. Nature 2013. 497: 127-131.
26. Tykocinski, L. O., Sinemus, A., Rezavandy, E., Weiland, Y., Baddeley, D., Cremer, C., Sonntag, S. et al., Epigenetic regulation of promiscuous gene expression in thymic medullary epithelial cells. Proc. Natl. Acad. Sci. U S A 2010. 107: 19426-19431.
27. Danso-Abeam, D., Staats, K. A., Franckaert, D., Van Den Bosch, L., Liston, A., Gray, D. H. and Dooley, J., Aire mediates thymic expression and tolerance of pancreatic antigens via an unconventional transcriptional mechanism. Eur. J. Immunol. 2013. 43: 75-84.
28. Schwab, S. R., Shugart, J. A., Horng, T., Malarkannan, S. and Shastri, N., Unanticipated antigens: translation initiation at CUG with leucine. PLoS Biol. 2004. 2: e366.
29. Apcher, S., Daskalogianni, C., Lejeune, F., Manoury, B., Imhoos, G., Heslop, L. and Fahraeus, R., Major source of antigenic peptides for the MHC class I pathway is produced during the pioneer round of mRNA translation. Proc. Natl. Acad. Sci. U S A 2011. 108: 11572-11577.
30. Boon, T. and Van Pel, A., T cell-recognized antigenic peptides derived from the cellular genome are not protein degradation products but can be generated directly by transcription and translation of short subgenic regions. A hypothesis. Immunogenetics 1989. 29: 75-79.
31. Blankenstein, T., Coulie, P. G., Gilboa, E. and Jaffee, E. M., The determinants of tumour immunogenicity. Nat. Rev. Cancer 2012. 12: 307-313.
32. Engels, B., Engelhard, V. H., Sidney, J., Sette, A., Binder, D. C., Liu, R. B., Kranz, D. M. et al., Relapse or eradication of cancer is predicted by peptide-major histocompatibility complex affinity. Cancer Cell 2013. 23: 516-526.
33. Kammertoens, T. and Blankenstein, T., It's the peptide-MHC affinity, stupid. Cancer Cell 2013. 23: 429-431.
34. Johnson, L. A., Morgan, R. A., Dudley, M. E., Cassard, L., Yang, J. C., Hughes, M. S., Kammula, U. S. et al., Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen. Blood 2009. 114: 535- 546.
35. Carey, T. E., Takahashi, T., Resnick, L. A., Oettgen, H. F. and Old, L. J., Cell surface antigens of human malignant melanoma: mixed hemadsorption assays for humoral immunity to cultured autologous melanoma cells. Proc. Natl. Acad. Sci. U S A 1976. 73: 3278-3282.
36. Rivoltini, L., Barracchini, K. C., Viggiano, V., Kawakami, Y., Smith, A., Mixon, A., Restifo, N. P. et al., Quantitative correlation between HLA class I allele expression and recognition of melanoma cells by antigen-specific cytotoxic T lymphocytes. Cancer Res. 1995. 55: 3149- 3157.
37. Popovic, J., Li, L. P., Kloetzel, P. M., Leisegang, M., Uckert, W. and Blankenstein, T., The only proposed T-cell epitope derived from the TELAML1 translocation is not naturally processed. Blood 2011. 118: 946-954.
38. Larribere, L., Khaled, M., Tartare-Deckert, S., Busca, R., Luciano, F., Bille, K., Valony, G. et al., PI3K mediates protection against TRAIL-induced apoptosis in primary human melanocytes. Cell Death Differ. 2004. 11: 1084-1091.
39. Steinle, A., Reinhardt, C., Jantzer, P. and Schendel, D. J., In vivo expansion of HLA-B35 alloreactive T cells sharing homologous T cell receptors: evidence for maintenance of an oligoclonally dominated allospecificity by persistent stimulation with an autologous MHC/peptide complex. J. Exp. Med. 1995. 181: 503-513.
40. Engels, B., Cam, H., Schuler, T., Indraccolo, S., Gladow, M., Baum, C., Blankenstein, T. et al., Retroviral vectors for high-level transgene expression in T lymphocytes. Hum. Gene Ther. 2003. 14: 1155-1168.
41. Sommermeyer, D. and Uckert, W., Minimal amino acid exchange in human TCR constant regions fosters improved function of TCR genemodified T cells. J. Immunol. 2010. 184: 6223-6231.