International Immunology Advance Access published online on July 2, 2007
International Immunology, doi:10.1093/intimm/dxm053
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T-cell activation results in microheterogeneous changes in glycosylation of CD45
1 Department of Pathology and Laboratory Medicine
2 Jonsson Comprehensive Cancer Center, UCLA School of Medicine, 10833 LeConte Avenue, Los Angeles, CA 90095, USA
3 Department of Cellular and Molecular Medicine, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093, USA
Correspondence to: Correspondence to: L. G. Baum; E-mail: lbaum{at}mednet.ucla.edu
During T-cell development and activation, dramatic changes occur in glycan structures that decorate cell-surface glycoproteins. These changes have been considered to be general cellular events that affect many glycans on many glycoproteins. For example, loss of sialic acid from core 1 O-glycans on T-cell surface glycoproteins CD45, CD43 and CD8, detected with peanut agglutinin (PNA), is a hallmark of immature thymocytes and activated peripheral T cells. Loss of cell-surface sialic acid during T-cell activation has been proposed to enhance TCR reactivity with antigen. However, CD4 T-cell activation also results in increased binding of the CZ-1 antibody that recognizes a sialic acid-containing epitope on CD45RB. This indicates that increased sialylation of the CZ-1 epitope occurs during CD4 T cell activation, and that loss of cell surface sialic acid during T-cell activation is a selective event rather than affecting all cell surface glycans. As specific glycans on specific glycoprotein backbones control critical events in T-cell maturation and survival, understanding mechanisms of selective glycoprotein glycosylation is important for regulating T-cell development and function. We define the sialylated O-glycan epitope recognized by CZ-1, and find that, paradoxically, CZ-1 and PNA binding are simultaneously increased on activated CD4+ T cells, demonstrating site-specific changes in CD45 sialylation. Moreover, we identify ST3Gal I as the sialyltransferase responsible for creating the CZ-1 epitope. Thus, changes in glycan structure during T-cell activation are microheterogeneous and unique to individual glycans on specific glycoproteins, implying that these glycans have precise functions in T-cell biology.
Keywords: glycosyltransferase, O-glycan, sialic acid
Transmitting editor: T. F. Tedder
Received 4 January 2007, accepted 10 April 2007.
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