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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Oct 1;88(19):8730–8734. doi: 10.1073/pnas.88.19.8730

Self peptide requirement for class II major histocompatibility complex allorecognition.

S Demotz 1, A Sette 1, K Sakaguchi 1, R Buchner 1, E Appella 1, H M Grey 1
PMCID: PMC52583  PMID: 1924332

Abstract

Using a dinitrophenylated and biotinylated peptide antigen, we have developed an affinity chromatography procedure to purify complexes of a given peptide species and a given class II major histocompatibility complex antigen away from class II molecules occupied by other peptides. We show that hen egg lysozyme peptide-I-Ed complexes purified according to this procedure have a greatly enhanced capacity to activate hen egg lysozyme-specific T cells but have lost the capacity to activate three different alloreactive T-cell hybridomas. These data demonstrate that the class II molecule in and of itself is not sufficient to activate alloreactive T cells. Rather, the data suggest that recognition of specific complexes formed between allo-class II and particular autologous peptides may be required. Alternatively, alloreactive T cells may be recognizing "empty" major histocompatibility complex molecules.

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Selected References

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  1. Adorini L., Sette A., Buus S., Grey H. M., Darsley M., Lehmann P. V., Doria G., Nagy Z. A., Appella E. Interaction of an immunodominant epitope with Ia molecules in T-cell activation. Proc Natl Acad Sci U S A. 1988 Jul;85(14):5181–5185. doi: 10.1073/pnas.85.14.5181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ashwell J. D., Chen C., Schwartz R. H. High frequency and nonrandom distribution of alloreactivity in T cell clones selected for recognition of foreign antigen in association with self class II molecules. J Immunol. 1986 Jan;136(2):389–395. [PubMed] [Google Scholar]
  3. Coeshott C. M., Chesnut R. W., Kubo R. T., Grammer S. F., Jenis D. M., Grey H. M. Ia-specific mixed leukocyte reactive T cell hybridomas: analysis of their specificity by using purified class II MHC molecules in synthetic membrane system. J Immunol. 1986 Apr 15;136(8):2832–2838. [PubMed] [Google Scholar]
  4. Demotz S., Grey H. M., Appella E., Sette A. Characterization of a naturally processed MHC class II-restricted T-cell determinant of hen egg lysozyme. Nature. 1989 Dec 7;342(6250):682–684. doi: 10.1038/342682a0. [DOI] [PubMed] [Google Scholar]
  5. Demotz S., Grey H. M., Sette A. The minimal number of class II MHC-antigen complexes needed for T cell activation. Science. 1990 Aug 31;249(4972):1028–1030. doi: 10.1126/science.2118680. [DOI] [PubMed] [Google Scholar]
  6. Eckels D. D., Gorski J., Rothbard J., Lamb J. R. Peptide-mediated modulation of T-cell allorecognition. Proc Natl Acad Sci U S A. 1988 Nov;85(21):8191–8195. doi: 10.1073/pnas.85.21.8191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Heath W. R., Hurd M. E., Carbone F. R., Sherman L. A. Peptide-dependent recognition of H-2Kb by alloreactive cytotoxic T lymphocytes. Nature. 1989 Oct 26;341(6244):749–752. doi: 10.1038/341749a0. [DOI] [PubMed] [Google Scholar]
  8. Hunt H. D., Pullen J. K., Dick R. F., Bluestone J. A., Pease L. R. Structural basis of Kbm8 alloreactivity. Amino acid substitutions on the beta-pleated floor of the antigen recognition site. J Immunol. 1990 Sep 1;145(5):1456–1462. [PubMed] [Google Scholar]
  9. Kappler J. W., Skidmore B., White J., Marrack P. Antigen-inducible, H-2-restricted, interleukin-2-producing T cell hybridomas. Lack of independent antigen and H-2 recognition. J Exp Med. 1981 May 1;153(5):1198–1214. doi: 10.1084/jem.153.5.1198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Krieger J. I., Karr R. W., Grey H. M., Yu W. Y., O'Sullivan D., Batovsky L., Zheng Z. L., Colón S. M., Gaeta F. C., Sidney J. Single amino acid changes in DR and antigen define residues critical for peptide-MHC binding and T cell recognition. J Immunol. 1991 Apr 1;146(7):2331–2340. [PubMed] [Google Scholar]
  11. Malissen M., Trucy J., Letourneur F., Rebaï N., Dunn D. E., Fitch F. W., Hood L., Malissen B. A T cell clone expresses two T cell receptor alpha genes but uses one alpha beta heterodimer for allorecognition and self MHC-restricted antigen recognition. Cell. 1988 Oct 7;55(1):49–59. doi: 10.1016/0092-8674(88)90008-6. [DOI] [PubMed] [Google Scholar]
  12. Marrack P., Kappler J. The T cell receptor. Science. 1987 Nov 20;238(4830):1073–1079. doi: 10.1126/science.3317824. [DOI] [PubMed] [Google Scholar]
  13. Matis L. A., Sorger S. B., McElligott D. L., Fink P. J., Hedrick S. M. The molecular basis of alloreactivity in antigen-specific, major histocompatibility complex-restricted T cell clones. Cell. 1987 Oct 9;51(1):59–69. doi: 10.1016/0092-8674(87)90010-9. [DOI] [PubMed] [Google Scholar]
  14. O'Sullivan D., Sidney J., Appella E., Walker L., Phillips L., Colón S. M., Miles C., Chesnut R. W., Sette A. Characterization of the specificity of peptide binding to four DR haplotypes. J Immunol. 1990 Sep 15;145(6):1799–1808. [PubMed] [Google Scholar]
  15. Ozaki S., Durum S. K., Muegge K., York-Jolley J., Berzofsky J. A. Production of T-T hybrids from T cell clones. Direct comparison between cloned T cells and T hybridoma cells derived from them. J Immunol. 1988 Jul 1;141(1):71–78. [PubMed] [Google Scholar]
  16. Ozato K., Mayer N., Sachs D. H. Hybridoma cell lines secreting monoclonal antibodies to mouse H-2 and Ia antigens. J Immunol. 1980 Feb;124(2):533–540. [PubMed] [Google Scholar]
  17. Panina-Bordignon P., Corradin G., Roosnek E., Sette A., Lanzavecchia A. Recognition by class II alloreactive T cells of processed determinants from human serum proteins. Science. 1991 Jun 14;252(5012):1548–1550. doi: 10.1126/science.1710827. [DOI] [PubMed] [Google Scholar]
  18. Sette A., Adorini L., Appella E., Colón S. M., Miles C., Tanaka S., Ehrhardt C., Doria G., Nagy Z. A., Buus S. Structural requirements for the interaction between peptide antigens and I-Ed molecules. J Immunol. 1989 Nov 15;143(10):3289–3294. [PubMed] [Google Scholar]
  19. Shimonkevitz R., Colon S., Kappler J. W., Marrack P., Grey H. M. Antigen recognition by H-2-restricted T cells. II. A tryptic ovalbumin peptide that substitutes for processed antigen. J Immunol. 1984 Oct;133(4):2067–2074. [PubMed] [Google Scholar]
  20. Shimonkevitz R., Kappler J., Marrack P., Grey H. Antigen recognition by H-2-restricted T cells. I. Cell-free antigen processing. J Exp Med. 1983 Aug 1;158(2):303–316. doi: 10.1084/jem.158.2.303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Viguier M., Dornmair K., Clark B. R., McConnell H. M. The invariant chain forms complexes with class II major histocompatibility complex molecules and antigenic peptides "in vivo". Proc Natl Acad Sci U S A. 1990 Sep;87(18):7170–7174. doi: 10.1073/pnas.87.18.7170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Vogel J. M., Davis A. C., McKinney D. M., McMillan M., Martin W. J., Goodenow R. S. Molecular characterization of the C3HfB/HeN H-2Kkm2 mutation. Implications for the molecular basis of alloreactivity. J Exp Med. 1988 Nov 1;168(5):1781–1800. doi: 10.1084/jem.168.5.1781. [DOI] [PMC free article] [PubMed] [Google Scholar]

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