T-cell activation results in microheterogeneous changes in glycosylation of CD45

Int Immunol. 2007 Jul;19(7):847-56. doi: 10.1093/intimm/dxm053. Epub 2007 Jul 2.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / metabolism
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Line
  • Epitopes, T-Lymphocyte
  • Glycosylation
  • Leukocyte Common Antigens / metabolism*
  • Lymphocyte Activation / physiology
  • Mice
  • N-Acetylneuraminic Acid / physiology
  • Peanut Agglutinin / metabolism
  • Sialyltransferases / metabolism
  • beta-Galactoside alpha-2,3-Sialyltransferase

Substances

  • Antibodies
  • Epitopes, T-Lymphocyte
  • Peanut Agglutinin
  • Sialyltransferases
  • Leukocyte Common Antigens
  • Ptprc protein, mouse
  • N-Acetylneuraminic Acid
  • beta-Galactoside alpha-2,3-Sialyltransferase