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Philosophical Transactions of the Royal Society B: Biological Sciences logoLink to Philosophical Transactions of the Royal Society B: Biological Sciences
. 2003 May 29;358(1433):875–877. doi: 10.1098/rstb.2003.1267

Generation of CD1 tetramers as a tool to monitor glycolipid-specific T cells.

Stephan D Gadola 1, Anastasios Karadimitris 1, Nathan R Zaccai 1, Mariolina Salio 1, Nicolas Dulphy 1, Dawn Shepherd 1, E Yvonne Jones 1, Vincenzo Cerundolo 1
PMCID: PMC1693178  PMID: 12803920

Abstract

CD1 molecules are beta(2)m-associated HLA class-I-like glycoproteins which have the unique ability to present glycolipid and phospholipid antigens to specific T lymphocytes. To study the biology of CD1 and its role in human disease we developed novel techniques for generation of recombinant CD1/lipid complexes by in vitro refolding. Fluorescent tetrameric complexes made from soluble recombinant CD1d/alpha-galactosylceramide complexes allowed highly sensitive and specific ex vivo and in vitro detection and functional characterization of novel human T-lymphocyte populations. Furthermore, protein crystals were obtained from soluble recombinant CD1b/beta(2)m-proteins loaded either with phosphatidylinositol or ganglioside GM2, which led to the first atomic structure determination of a CD1/lipid complex. The analysis of these crystal structures clarified how CD1b molecules can bind lipid ligands of different size, and revealed a broader spectrum of potential CD1b ligands than previously predicted.

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Selected References

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  1. Apostolou I., Takahama Y., Belmant C., Kawano T., Huerre M., Marchal G., Cui J., Taniguchi M., Nakauchi H., Fournié J. J. Murine natural killer T(NKT) cells [correction of natural killer cells] contribute to the granulomatous reaction caused by mycobacterial cell walls. Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):5141–5146. doi: 10.1073/pnas.96.9.5141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beckman E. M., Porcelli S. A., Morita C. T., Behar S. M., Furlong S. T., Brenner M. B. Recognition of a lipid antigen by CD1-restricted alpha beta+ T cells. Nature. 1994 Dec 15;372(6507):691–694. doi: 10.1038/372691a0. [DOI] [PubMed] [Google Scholar]
  3. Benlagha K., Weiss A., Beavis A., Teyton L., Bendelac A. In vivo identification of glycolipid antigen-specific T cells using fluorescent CD1d tetramers. J Exp Med. 2000 Jun 5;191(11):1895–1903. doi: 10.1084/jem.191.11.1895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Benlagha Kamel, Kyin Tim, Beavis Andrew, Teyton Luc, Bendelac Albert. A thymic precursor to the NK T cell lineage. Science. 2002 Apr 19;296(5567):553–555. doi: 10.1126/science.1069017. [DOI] [PubMed] [Google Scholar]
  5. Davodeau F., Peyrat M. A., Necker A., Dominici R., Blanchard F., Leget C., Gaschet J., Costa P., Jacques Y., Godard A. Close phenotypic and functional similarities between human and murine alphabeta T cells expressing invariant TCR alpha-chains. J Immunol. 1997 Jun 15;158(12):5603–5611. [PubMed] [Google Scholar]
  6. Gadola Stephan D., Dulphy Nicolas, Salio Mariolina, Cerundolo Vincenzo. Valpha24-JalphaQ-independent, CD1d-restricted recognition of alpha-galactosylceramide by human CD4(+) and CD8alphabeta(+) T lymphocytes. J Immunol. 2002 Jun 1;168(11):5514–5520. doi: 10.4049/jimmunol.168.11.5514. [DOI] [PubMed] [Google Scholar]
  7. Gadola Stephan D., Zaccai Nathan R., Harlos Karl, Shepherd Dawn, Castro-Palomino Julio C., Ritter Gerd, Schmidt Richard R., Jones E. Yvonne, Cerundolo Vincenzo. Structure of human CD1b with bound ligands at 2.3 A, a maze for alkyl chains. Nat Immunol. 2002 Jul 15;3(8):721–726. doi: 10.1038/ni821. [DOI] [PubMed] [Google Scholar]
  8. Gumperz J. E., Roy C., Makowska A., Lum D., Sugita M., Podrebarac T., Koezuka Y., Porcelli S. A., Cardell S., Brenner M. B. Murine CD1d-restricted T cell recognition of cellular lipids. Immunity. 2000 Feb;12(2):211–221. doi: 10.1016/s1074-7613(00)80174-0. [DOI] [PubMed] [Google Scholar]
  9. Karadimitris A., Gadola S., Altamirano M., Brown D., Woolfson A., Klenerman P., Chen J. L., Koezuka Y., Roberts I. A., Price D. A. Human CD1d-glycolipid tetramers generated by in vitro oxidative refolding chromatography. Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3294–3298. doi: 10.1073/pnas.051604498. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Klenerman Paul, Cerundolo Vincenzo, Dunbar P. Rod. Tracking T cells with tetramers: new tales from new tools. Nat Rev Immunol. 2002 Apr;2(4):263–272. doi: 10.1038/nri777. [DOI] [PubMed] [Google Scholar]
  11. Kronenberg Mitchell, Gapin Laurent. The unconventional lifestyle of NKT cells. Nat Rev Immunol. 2002 Aug;2(8):557–568. doi: 10.1038/nri854. [DOI] [PubMed] [Google Scholar]
  12. Lantz O., Bendelac A. An invariant T cell receptor alpha chain is used by a unique subset of major histocompatibility complex class I-specific CD4+ and CD4-8- T cells in mice and humans. J Exp Med. 1994 Sep 1;180(3):1097–1106. doi: 10.1084/jem.180.3.1097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Matsuda J. L., Naidenko O. V., Gapin L., Nakayama T., Taniguchi M., Wang C. R., Koezuka Y., Kronenberg M. Tracking the response of natural killer T cells to a glycolipid antigen using CD1d tetramers. J Exp Med. 2000 Sep 4;192(5):741–754. doi: 10.1084/jem.192.5.741. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Moody D. B., Reinhold B. B., Guy M. R., Beckman E. M., Frederique D. E., Furlong S. T., Ye S., Reinhold V. N., Sieling P. A., Modlin R. L. Structural requirements for glycolipid antigen recognition by CD1b-restricted T cells. Science. 1997 Oct 10;278(5336):283–286. doi: 10.1126/science.278.5336.283. [DOI] [PubMed] [Google Scholar]
  15. Moody D. B., Ulrichs T., Mühlecker W., Young D. C., Gurcha S. S., Grant E., Rosat J. P., Brenner M. B., Costello C. E., Besra G. S. CD1c-mediated T-cell recognition of isoprenoid glycolipids in Mycobacterium tuberculosis infection. Nature. 2000 Apr 20;404(6780):884–888. doi: 10.1038/35009119. [DOI] [PubMed] [Google Scholar]
  16. Naidenko O. V., Maher J. K., Ernst W. A., Sakai T., Modlin R. L., Kronenberg M. Binding and antigen presentation of ceramide-containing glycolipids by soluble mouse and human CD1d molecules. J Exp Med. 1999 Oct 18;190(8):1069–1080. doi: 10.1084/jem.190.8.1069. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Porcelli S. A., Modlin R. L. The CD1 system: antigen-presenting molecules for T cell recognition of lipids and glycolipids. Annu Rev Immunol. 1999;17:297–329. doi: 10.1146/annurev.immunol.17.1.297. [DOI] [PubMed] [Google Scholar]
  18. Porcelli S. A. The CD1 family: a third lineage of antigen-presenting molecules. Adv Immunol. 1995;59:1–98. doi: 10.1016/s0065-2776(08)60629-x. [DOI] [PubMed] [Google Scholar]
  19. Shamshiev A., Donda A., Carena I., Mori L., Kappos L., De Libero G. Self glycolipids as T-cell autoantigens. Eur J Immunol. 1999 May;29(5):1667–1675. doi: 10.1002/(SICI)1521-4141(199905)29:05<1667::AID-IMMU1667>3.0.CO;2-U. [DOI] [PubMed] [Google Scholar]
  20. Shamshiev A., Gober H-J, Donda A., Mazorra Z., Mori L., De Libero G. Presentation of the same glycolipid by different CD1 molecules. J Exp Med. 2002 Apr 15;195(8):1013–1021. doi: 10.1084/jem.20011963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sieling P. A., Chatterjee D., Porcelli S. A., Prigozy T. I., Mazzaccaro R. J., Soriano T., Bloom B. R., Brenner M. B., Kronenberg M., Brennan P. J. CD1-restricted T cell recognition of microbial lipoglycan antigens. Science. 1995 Jul 14;269(5221):227–230. doi: 10.1126/science.7542404. [DOI] [PubMed] [Google Scholar]
  22. Sumida T., Sakamoto A., Murata H., Makino Y., Takahashi H., Yoshida S., Nishioka K., Iwamoto I., Taniguchi M. Selective reduction of T cells bearing invariant V alpha 24J alpha Q antigen receptor in patients with systemic sclerosis. J Exp Med. 1995 Oct 1;182(4):1163–1168. doi: 10.1084/jem.182.4.1163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Townsend A. R., Rothbard J., Gotch F. M., Bahadur G., Wraith D., McMichael A. J. The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell. 1986 Mar 28;44(6):959–968. doi: 10.1016/0092-8674(86)90019-x. [DOI] [PubMed] [Google Scholar]
  24. Wilson S. B., Kent S. C., Patton K. T., Orban T., Jackson R. A., Exley M., Porcelli S., Schatz D. A., Atkinson M. A., Balk S. P. Extreme Th1 bias of invariant Valpha24JalphaQ T cells in type 1 diabetes. Nature. 1998 Jan 8;391(6663):177–181. doi: 10.1038/34419. [DOI] [PubMed] [Google Scholar]

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