The role of asparagine-linked oligosaccharides in cellular recognition by thymic lymphocytes. Effects of tunicamycin on the mixed lymphocyte reaction

Gerald Warren Hart

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Abstract

A large body of experimental evidence indicates that both the humoral and cellular immune responses are regulated by a complex network of cellular interactions mediated by cell surface glycoproteins encoded by the major histocompatibility gene complex. Even though many of the serologically defined specificities of these glycoproteins are on the polypeptide portions of these molecules, virtually nothing is known about the role of their saccharide moieties in the specific cell-cell interactions of lymphocytes. The possible involvement of asparagine-linked saccharide moieties in lymphocyte mediated cellular interactions has been investigated using the glycosylation inhibitor tunicamycin and the one-way mixed lymphocyte assay, an in vitro analogue of the inductive phase of allograft rejection. It is well established that the I region-associated antigens of the mouse, which are asparagine-linked glycoproteins, are critical to the process of stimulation of thymic lymphocytes in these assays. The results of these studies indicate the following. Pretreatment of allogeneic stimulator cells with tunicamycin prevents their induction of a primary blastogenic response by thymic lymphocytes. The inhibition is due to the direct action of tunicamycin on the stimulator cells. The tunicamycin treatment of stimulator cells blocks the glycosylation of I region-associated and H-2 polypeptides but not their synthesis or insertion into the plasma membrane. Mitomycin C-treated stimulator cells, which actively induce a mixed lymphocyte response in the absence of tunicamycin treatment, are inert with respect to DNA, protein, and glycoprotein biosynthesis. These data strongly suggest that asparagine-linked saccharides on the surfaces of stimulator cells play an essential role in the cell-cell interactions which elicit a blastogenic response in allogeneic thymic lymphocytes.

Original languageEnglish (US)
Pages (from-to)151-158
Number of pages8
JournalJournal of Biological Chemistry
Volume257
Issue number1
StatePublished - 1982

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Tunicamycin
Mixed Lymphocyte Culture Test
Lymphocytes
Asparagine
Oligosaccharides
Glycosylation
Glycoproteins
Cell Communication
Assays
Peptides
Biosynthesis
Membrane Glycoproteins
Complex networks
Protein Biosynthesis
Mitomycin
Cell membranes
Lymphocyte Activation
Humoral Immunity
Major Histocompatibility Complex
Cellular Immunity

ASJC Scopus subject areas

  • Biochemistry

Cite this

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abstract = "A large body of experimental evidence indicates that both the humoral and cellular immune responses are regulated by a complex network of cellular interactions mediated by cell surface glycoproteins encoded by the major histocompatibility gene complex. Even though many of the serologically defined specificities of these glycoproteins are on the polypeptide portions of these molecules, virtually nothing is known about the role of their saccharide moieties in the specific cell-cell interactions of lymphocytes. The possible involvement of asparagine-linked saccharide moieties in lymphocyte mediated cellular interactions has been investigated using the glycosylation inhibitor tunicamycin and the one-way mixed lymphocyte assay, an in vitro analogue of the inductive phase of allograft rejection. It is well established that the I region-associated antigens of the mouse, which are asparagine-linked glycoproteins, are critical to the process of stimulation of thymic lymphocytes in these assays. The results of these studies indicate the following. Pretreatment of allogeneic stimulator cells with tunicamycin prevents their induction of a primary blastogenic response by thymic lymphocytes. The inhibition is due to the direct action of tunicamycin on the stimulator cells. The tunicamycin treatment of stimulator cells blocks the glycosylation of I region-associated and H-2 polypeptides but not their synthesis or insertion into the plasma membrane. Mitomycin C-treated stimulator cells, which actively induce a mixed lymphocyte response in the absence of tunicamycin treatment, are inert with respect to DNA, protein, and glycoprotein biosynthesis. These data strongly suggest that asparagine-linked saccharides on the surfaces of stimulator cells play an essential role in the cell-cell interactions which elicit a blastogenic response in allogeneic thymic lymphocytes.",
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