The sialyltransferase ST3Gal-I is not required for regulation of CD8-class I MHC binding during T cell development

J Immunol. 2006 Jun 15;176(12):7421-30. doi: 10.4049/jimmunol.176.12.7421.

Abstract

The CD8 coreceptor plays a crucial role in thymocyte and T cell sensitivity by binding to class I MHC and recruiting downstream signaling molecules to the TCR. Previous studies reported considerable changes in TCR-independent CD8/class I MHC binding (i.e., CD8 noncognate interactions) during T cell development, changes that correlated with altered glycosylation of surface molecules. In particular, expression of the sialyltransferase ST3Gal-I has been proposed as a critical factor regulating the attenuation of CD8 avidity during the double-positive to CD8 single-positive progression. This hypothesis is strengthened by the fact that ST3Gal-I(-/-) animals show a profound disregulation of CD8 T cell homeostasis. In contrast to this model, however, we report in this study that ST3Gal-I deficiency had no detectable impact on CD8 noncognate binding to multimeric peptide/MHC class I ligands at any stage of thymocyte development. We also found that the susceptibility to CD8-induced cell death is not markedly influenced by ST3Gal-I deficiency. Thus, the profound effects of ST3Gal-I on CD8 T cell survival evidently do not involve a role for this enzyme in controlling CD8-class I binding.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Apoptosis / immunology
  • CD8 Antigens / biosynthesis
  • CD8 Antigens / immunology
  • CD8 Antigens / metabolism*
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / enzymology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology*
  • Histocompatibility Antigens Class I / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Protein Binding / genetics
  • Protein Binding / immunology
  • Receptors, Antigen, T-Cell / metabolism*
  • Sialic Acids / metabolism
  • Sialyltransferases* / deficiency
  • Sialyltransferases* / genetics
  • Sialyltransferases* / metabolism
  • Sialyltransferases* / physiology
  • T-Lymphocyte Subsets / cytology*
  • T-Lymphocyte Subsets / enzymology
  • T-Lymphocyte Subsets / immunology
  • Thymus Gland / cytology*
  • Thymus Gland / enzymology
  • Thymus Gland / immunology
  • beta-Galactoside alpha-2,3-Sialyltransferase

Substances

  • CD8 Antigens
  • CD8 receptor
  • Histocompatibility Antigens Class I
  • Receptors, Antigen, T-Cell
  • Sialic Acids
  • Sialyltransferases
  • beta-Galactoside alpha-2,3-Sialyltransferase