Abstract
CLASS II histocompatibility molecules associate with peptides derived from antigens that are processed in endocytic compartments. Antigen presentation to class II-restricted T cells generally requires newly synthesized class II molecules1, associated invariant chain2,3, and HLA-DM4,5. Exceptions to these rules have been reported6–10, but without description of an underlying mechanism. Here we show that presentation of immunodominant epitopes in the haemagglutinin protein of influenza virus and in myeiin basic protein correlates with recycling of surface HLA-DR molecules. Truncation of either one of the α or β cytoplasmic tails virtually eliminated internalization of HLA-DR molecules and presentation of haemagglutinin from inactive virus particles. In contrast, the invariant chain-dependent presentation of matrix antigen from the same virus particles was unaffected by these truncations. Thus HLA-DR cytoplasmic tails are not required for the conventional presentation pathway, but jointly contribute a signal for an alternative pathway involving internalization of HLA-DR molecules.
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References
Davidson, H. W., Reid, P. A., Lanzavecchia, A. & Watts, C. Cell 67, 105–116 (1991).
Viviile, S. et al. Cell 72, 635–648 (1993).
Bikoff, E. K. et al. J. exp. Med. 177, 1699–1712 (1993).
Morris, P. et al. Nature 368, 551–554 (1994).
Fling, S. P., Arp, B. & Pious, D. Nature 368, 554–558 (1994).
Kakiuchi, T., Watanabe, M., Hozumi, N. & Nariuchi, H. J. Immun. 145, 1653–1658 (1990).
Nadimi, F. et al. Eur. J. Immun. 21, 1255–1263 (1991).
Pinet, V., Malnati, M. S. & Long, E. O. J. Immun. 152, 4852–4860 (1994).
Brooks, A. G., Campbell, P. L., Reynolds, P., Gautam, A. M. & McCluskey, J. J. Immun. 153, 5382–5392 (1994).
Stebbins, C. C., Loss, G. E. Jr, Elias, C. G., Chervonsky, A. & Sant, A. J. J. exp. Med. 181, 223–234 (1995).
Cresswell, P. A. Rev. Immun. 12, 259–293 (1994).
Adorini, L., Appella, E., Doria, G., Cardinaux, F. & Nagy, Z. A. Nature 342, 800–803 (1989).
Harding, C. V. & Unanue, E. R. J. Immun. 142, 12–19 (1989).
Klausner, R. D. et al. J. biol. Chem. 258, 4715–4724 (1983).
Roche, P. A., Teletski, C. L., Stang, E., Bakke, O. & Long, E. O. Proc. natn. Acad. Sci. U.S.A. 90, 8581–8585 (1993).
Simonsen, A., Momburg, F., Drexler, J., Hammerling, G. J. & Bakke, O. Int. Immun. 5, 903–917 (1993).
Reid, P. A. & Watts, C. Immunology 77, 539–542 (1992).
Rothbard, J. B. & Gefter, M. L. A. Rev. Immun. 9, 527–565 (1991).
Nabavi, N. et al. J. Immun. 142, 1444–1447 (1989).
St-Pierre, Y., Nabavi, N., Ghogawala, Z., Glimcher, L. H. & Watts, T. H. J. Immun. 143, 808–812 (1989).
Riccio, P., Bobba, A., Romito, E., Minetola, M. & Quagliariello, E. Neuroreport 5, 689–692 (1994).
Bodmer, H., Viville, S., Benoist, C. & Mathis, D. Science 263, 1284–1286 (1994).
Lanzavecchia, A., Reid, P. A. & Watts, C. Nature 357, 249–252 (1992).
Nelson, C. A., Petzold, S. J. & Unanue, E. R. Nature 371, 250–252 (1994).
Germain, R. N. & Rinker, A. G. Jr, Nature 363, 725–728 (1993).
Chicz, R. M. et al. Nature 358, 764–768 (1992).
Long, E. O., LaVaute, T., Pinet, V. & Jaraquemada, D. J. Immun. 153, 1487–1494 (1994).
Davis, J. E. & Cresswell, P. J. Immun. 144, 990–997 (1990).
Radka, S. F., Machamer, C. E. & Cresswell, P. Hum. Immun. 10, 177–186 (1984).
Martin, R. et al. J. Immun. 148, 1359–1366 (1992).
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Pinet, V., Vergelli, M., Martini, R. et al. Antigen presentation mediated by recycling of surface HLA-DR molecules. Nature 375, 603–606 (1995). https://doi.org/10.1038/375603a0
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DOI: https://doi.org/10.1038/375603a0
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