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Invariant chain association with HLA-DR molecules inhibits immunogenic peptide binding

Abstract

CLASS II major histocompatibility complex (MHC) molecules are heterodimeric cell surface glycoproteins which bind and present immunogenic peptides to T lymphocytes. Such peptides are normally derived from protein antigens internalized and proteolytically degraded by the antigen-presenting cell1. Class I MHC molecules also bind immunogenic peptides, but these are derived from proteins synthesized within the target cell2. Whereas class I molecules seem to bind peptides in the endoplasmic reticulum3–5, class II molecules are thought to bind peptides late in transport. Intracellular class II molecules associate in the endoplasmic reticulum with a third glycoprotein, the invariant (I) chain, which is proteolytically removed before cell surface expression of the αβ class II heterodimer6,7. It has been suggested that the I chain prevents peptides from associating with class II molecules early in transport8. Preventing such binding until the class II molecules enter an endosomal compartment could maintain the functional dichotomy between class I and class II MHC molecules. We have examined the ability of I chain-associated HLA-DR5 moleculesto bind a well characterized influenza haemagglutinin-derived peptide (HAp). The results show that whereas mature HLA-DR αβ dimers effectively bind this peptide, the I chain-associated form does not.

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References

  1. Unanue, E. R. A. Rev. Immun. 2, 395–428 (1984).

    Article  CAS  Google Scholar 

  2. Townsend, A. R. M. & Bodmer, H. A. Rev. Immun. 7, 601–624 (1989).

    Article  CAS  Google Scholar 

  3. Nuchtern, J. G., Bonifacino, J. S., Biddison, W. E. & Klausner, R. D. Nature 339, 223–226 (1989).

    Article  ADS  CAS  Google Scholar 

  4. Yewdell, J. W. & Bennink, J. R. Science 244, 1072–1075 (1989).

    Article  ADS  CAS  Google Scholar 

  5. Townsend, A. R. M. et al. Nature 340, 443–448 (1989).

    Article  ADS  CAS  Google Scholar 

  6. Machamer, C. E. & Cresswell, P. J. Immun. 129, 2564–2569 (1982).

    CAS  PubMed  Google Scholar 

  7. Blum, J. S. & Cresswell, P. Proc. natn. Acad. Sci. U.S.A. 85, 3975–3979 (1988).

    Article  ADS  CAS  Google Scholar 

  8. Elliot, W. L. Stille, C. J., Thomas, L. J. & Humphreys, R. E. J. Immun. 138, 2949–2952 (1987).

    Google Scholar 

  9. Roche, P. A. & Cresswell, P. J. Immun. 144, 1849–1856 (1990).

    CAS  PubMed  Google Scholar 

  10. Kelner, D. N. & Cresswell, P. J. Immun. 137, 2632–2639 (1986).

    CAS  PubMed  Google Scholar 

  11. Cresswell, P. Proc. natn. Acad. Sci. U.S.A. 82, 8188–8192 (1985).

    Article  ADS  CAS  Google Scholar 

  12. Takahashi, H., Cease, K. B. & Berzofsky, J. A. J. Immun. 142, 2221–2229 (1989).

    CAS  PubMed  Google Scholar 

  13. Guagliardi, L. E. et al. Nature 343, 133–139 (1990).

    Article  ADS  CAS  Google Scholar 

  14. Cresswell, P., Blum, J. S., Kelner, D. N. & Marks, M. S. CRC Crit. Rev. Immun. 7, 31–54 (1987).

    CAS  Google Scholar 

  15. Lampson, L. A. & Levy, R. J. Immun. 125, 293–299 (1980).

    CAS  Google Scholar 

  16. Cresswell, P. & Blum, J. S. Processing and Presentation of Antigens (eds Pernis, B., Silverstein, S. C. & Vogel, H. J.) 43–51 (Academic, San Diego, 1988).

    Google Scholar 

  17. Guy, K., van Heyningen, V., Cohen, B. B., Deane, D. L. & Steel, C. M. Eur. J. Immun. 12, 942–948 (1982).

    Article  CAS  Google Scholar 

  18. Machamer, C. E. & Cresswell, P. Proc. natn. Acad. Sci. U.S.A. 81, 1287–1291 (1984).

    Article  ADS  CAS  Google Scholar 

  19. Radka, S. F., Machamer, C. E. & Cresswell, P. Hum. Immun. 10, 177–188 (1984).

    Article  CAS  Google Scholar 

  20. Marks, M. S., Blum, J. S. & Cresswell, P. J. Cell Biol. (in the press).

Download references

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Roche, P., Cresswell, P. Invariant chain association with HLA-DR molecules inhibits immunogenic peptide binding. Nature 345, 615–618 (1990). https://doi.org/10.1038/345615a0

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