T-cell activation results in microheterogeneous changes in glycosylation of CD45.
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.
Hernandez
Joseph D
JD
Department of Pathology and Laboratory Medicine, UCLA School of Medicine, 10833 LeConte Avenue, Los Angeles, CA 90095, USA..
Klein
Jeffrey
J
Van Dyken
Stephen J
SJ
Marth
Jamey D
JD
Baum
Linda G
LG
D000818:Animals; D000906:Antibodies / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte; D006031:Glycosylation; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000502:physiology; D051379:Mice; D019158:N-Acetylneuraminic Acid / Q000502:physiology; D019887:Peanut Agglutinin / Q000378:metabolism; D012799:Sialyltransferases / Q000378:metabolism; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
D000906:Antibodies; D018984:Epitopes, T-Lymphocyte; D019887:Peanut Agglutinin; D012799:Sialyltransferases; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse; D019158:N-Acetylneuraminic Acid; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase