Abstract
FUNCTIONAL, morphological and biochemical evidence indicates that class II major histocompatibility complex (MHC) molecules associate with processed peptides during biosynthesis1–9. Peptide/MHC complexes in living cells have been reported to be less stable than similar complexes generated in vitro, which has led to the suggestion that there may be a peptide exchange mechanism operating in vivo l0–12. Although this could increase the capacity for binding incoming antigens, it would reduce the efficacy of processed antigenic peptides by exchanging these for self peptides. Here we measure the half-life of peptide/class II complexes in human antigen-presenting cells and find that it is very similar to the half-life of class II molecules themselves, indicating that peptides are bound irreversibly under physiological conditions. Thus class II MHC retains long-term 'memory' of past encounters with antigen to maximize the opportunity for T cell/antigen-presenting cell interaction.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Adorini, L., Ullrich, S. J., Appella, E. & Fuchs, S. Nature 346, 63–67 (1990).
St Pierre, Y. & Watts, T. H. J. Immun. 145, 812–818 (1990).
Neefjes, J. J., Stollorz, V., Peters, P. J., Geuze, H. J. & Ploegh, H. L. Cell 61, 171–183 (1990).
Peters, P. J., Neefjes, J. J., Oorschot, V., Ploegh, H. L. & Geuze, H. J. Nature 349, 669–676 (1991).
Davidson, H. W., Reid, P. A., Lanzavecchia, A. & Watts, C. Cell 67, 105–116 (1991).
Teyton, L. et al. Nature 348, 39–44 (1990).
Germain, R. N. & Hendrix, L. R. Nature 353, 134–139 (1991).
Roche, P. A. & Cresswell, P. Nature 345, 615–618 (1990).
Neefjes, J. J. & Ploegh, H. L. EMBO J. 11, 411–416 (1992).
Pernis, B. Immun. Today 6, 45–49 (1985).
Harding, C. W., Roof, R. W. & Unanue, E. R. Proc. natn. Acad. Sci. U.S.A. 86, 4230–4234 (1989).
Adorini, L., Appella, E., Doria, G., Cardinaux, F. & Nagy, Z. A. Nature 342, 800–803 (1990).
Lanzavecchia, A. Immunol. Rev. 99, 39–51 (1987).
Davidson, H. W. & Watts, C. J. Cell Biol. 109, 85–92 (1989).
Mathis, L. A., Glimcher, L. H., Paul, W. E. & Schwartz, R. H. Proc. natn. Acad. Sci. U.S.A. 80, 6019–23 (1983).
Panina-Bordignon, P. et al. Eur. J. Immun. 19, 2237–2242 (1989).
Panina-Bordignon, P., Corradin, G., Roosnek, E., Sette, A. & Lanzavecchia, A. Science 252, 1548–1550 (1991).
Davis, J. & Cresswell, P. J. Immun. 144, 990–997 (1990).
Sadegh-Nasseri, S. & Germain, R. N. Nature 353, 167–170 (1991).
Stern, L. J. & Wiley, D. C. Cell 68, 465–477 (1992).
Thompson, J. A., Lav, A. L. & Cunnigham, D. D. Biochemistry 26, 743–750 (1983).
Bretscher, M. S. & Lutter, R. EMBO J. 7, 4087–4092 (1988).
Reid, P. A. & Watts, C. Nature 346, 655–657 (1990).
Harding, C. V. & Unanue, E. R. J. Immun. 142, 12–19 (1989).
Jensen, P. E. J. Immun. 143, 420–425 (1989).
Lee, J. M. & Watts, T. H. J. Immun. 144, 1829–1834 (1990).
Roche, P. & Cresswell, P. J. Immun. 144, 1849–56 (1990).
Rothbard, J. B. & Gefter, M. L. A. Rev. Immun. 9, 527–565 (1991).
Nygard, N. R. et al. J. exp. Med. 174, 243–251 (1991).
Busch, R., Strang, G., Howland, K. & Rothbard, J. B. Int. Immun. 2, 443–451 (1990).
Pedrazzini, T., Sette, A., Albertson, M. & Grey, H. M. J. Immun. 146, 3496–3501 (1991).
Puré, E. et al. J. Exp. Med. 172, 1459–1469 (1990).
Kampgen, E. et al. Proc. natn. Acad. Sci. U.S.A. 88, 3014–3018 (1991).
Rippmann, F., Taylor, W. R., Rothbard, J. B. & Green, N. M. EMBO J. 10, 1053–1059 (1991).
Flajnik, M. F., Canel, C., Kramer, J. & Kasahara, M. Proc. natn. Acad. Sci. U.S.A. 88, 537–541 (1991).
Flynn, G. C., Pohl, J., Flocco, M. T. & Rothman, J. E. Nature 353, 726–730 (1991).
Lanzavecchia, A. Nature 314, 537–539 (1985).
Jensen, P. J. exp. Med. 171, 1779–1784 (1990).
Guy, K., Van Heyningen, V., Cohen, B. B., Dean, D. L. & Steel, C. M. Eur. J. Immun. 12, 942–948 (1982).
Fraker, P. J. & Speck, J. C. Biochem. biophys. Res. Commun. 80, 849–857 (1978).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lanzavecchia, A., Reid, P. & Watts, C. Irreversible association of peptides with class II MHC molecules in living cells. Nature 357, 249–252 (1992). https://doi.org/10.1038/357249a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/357249a0
This article is cited by
-
Analysis of peptide-SLA binding by establishing immortalized porcine alveolar macrophage cells with different SLA class II haplotypes
Veterinary Research (2018)
-
Rapid loss of early antigen-presenting activity of lymph node dendritic cells against Ag85A protein following Mycobacterium bovis BCG infection
BMC Immunology (2018)
-
HLA-DM captures partially empty HLA-DR molecules for catalyzed removal of peptide
Nature Immunology (2011)
-
Differences in the risk of celiac disease associated with HLA-DQ2.5 or HLA-DQ2.2 are related to sustained gluten antigen presentation
Nature Immunology (2009)
-
Initiation of primary anti-vaccinia virus immunity in vivo
Immunologic Research (2007)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.
