This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Van Dyken, S. J.
Right arrow Articles by Marth, J. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Van Dyken, S. J.
Right arrow Articles by Marth, J. D.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, February 2007, p. 1096-1111, Vol. 27, No. 3
0270-7306/07/$08.00+0     doi:10.1128/MCB.01750-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Structural and Mechanistic Features of Protein O Glycosylation Linked to CD8+ T-Cell Apoptosis{triangledown} ,{dagger}

Steven J. Van Dyken, Ryan S. Green, and Jamey D. Marth*

Howard Hughes Medical Institute and Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0625

Received 15 September 2006/ Returned for modification 8 October 2006/ Accepted 4 November 2006

CD8+ T-cell apoptosis is essential for the contraction phase of the immune response, yet the initiating signals and precise pathways involved are unresolved. The ST3Gal-I sialyltransferase is a candidate mechanistic component and catalyzes sialic acid addition to core 1 O-glycans during protein O glycosylation. ST3Gal-I inactivation or enzymatic removal of its product renders CD8+ T cells, but not CD4+ T cells, susceptible to apoptosis by differential cross-linking of O-glycoproteins in the absence of interleukin-2 and T-cell receptor (TCR) signaling. This results in caspase activation, DNA fragmentation, and phosphatidylserine externalization prior to cell death. We further show that ST3Gal-I function is regulated by a posttranscriptional mechanism operating distal to Golgi core 2 O glycosylation and is invariably linked to CD8+ T-cell contraction following viral (lymphocytic choriomeningitis virus) infection and bacterial (staphylococcal enterotoxin B) antigen immunization. The mechanism does not involve the ST3Gal-I substrate CD43 or core 2 O-glycan induction and overcomes the ability of Bcl-2 to inhibit the contraction phase in vivo. Loss of ST3Gal-I function further reduces Bim-deficient CD8+ T-cell accumulation without diminishing apoptotic sensitivity. We propose that an endogenous lectin activates an apoptotic pathway constructed in CD8+ T cells following TCR stimulation and enables contraction upon attenuation of immune signaling.

* Corresponding author. Mailing address: Howard Hughes Medical Institute and Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0625. Phone: (858) 534-6526. Fax: (858) 534-6724. E-mail: jmarth{at}ucsd.edu.

{triangledown} Published ahead of print on 13 November 2006.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, February 2007, p. 1096-1111, Vol. 27, No. 3
0270-7306/07/$08.00+0     doi:10.1128/MCB.01750-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Benoist, H., Culerrier, R., Poiroux, G., Segui, B., Jauneau, A., Van Damme, E. J. M., Peumans, W. J., Barre, A., Rouge, P. (2009). Two structurally identical mannose-specific jacalin-related lectins display different effects on human T lymphocyte activation and cell death. J. Leukoc. Biol. 86: 103-114 [Abstract] [Full Text]  
  • Tao, S.-C., Li, Y., Zhou, J., Qian, J., Schnaar, R. L, Zhang, Y., Goldstein, I. J, Zhu, H., Schneck, J. P (2008). Lectin microarrays identify cell-specific and functionally significant cell surface glycan markers. Glycobiology 18: 761-769 [Abstract] [Full Text]  
  • Marino, J. H, Tan, C., Davis, B., Han, E.-S., Hickey, M., Naukam, R., Taylor, A., Miller, K. S, Van De Wiele, C J., Teague, T K. (2008). Disruption of thymopoiesis in ST6Gal I-deficient mice. Glycobiology 18: 719-726 [Abstract] [Full Text]  
  • Alavi, A., Axford, J. S. (2008). Sweet and sour: the impact of sugars on disease. Rheumatology (Oxford) 47: 760-770 [Abstract] [Full Text]  
  • Tenno, M., Ohtsubo, K., Hagen, F. K., Ditto, D., Zarbock, A., Schaerli, P., von Andrian, U. H., Ley, K., Le, D., Tabak, L. A., Marth, J. D. (2007). Initiation of Protein O Glycosylation by the Polypeptide GalNAcT-1 in Vascular Biology and Humoral Immunity. Mol. Cell. Biol. 27: 8783-8796 [Abstract] [Full Text]  
  • Hernandez, J. D., Klein, J., Van Dyken, S. J., Marth, J. D., Baum, L. G. (2007). T-cell activation results in microheterogeneous changes in glycosylation of CD45. Int Immunol 0: dxm053v1- [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»