Progesterone induces a switch in oligosaccharyltransferase isoform expression: Consequences on IgG N-glycosylation

M. Belén Prados, Julia La Blunda, J. Szekeres-Barthó, Julio Caramelo, Silvia Miranda

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The presence of additional N-glycans in the Fab region of IgG has shown to dramatically modify the properties and functionality of these molecules including changes in antibody affinity and stability. However, the underlying molecular mechanism responsible for the presence or absence of these glycans remains unknown. Polypeptide N-linked glycosylation is catalyzed in the lumen of the endoplasmic reticulum by the oligosaccharyltransferase complex. Mammalian cells can express two isoforms of the oligosaccharyltransferase catalytic subunit (STT3-A and STT3-B), which are endowed with distinct enzymatic properties. In this work we employed a murine hybridoma cell culture to study whether the expression of STT3 isoforms could be modulated by progesterone, thus altering the pattern of IgG N-glycosylation. We found that progesterone induces a switch of STT3 isoform expression, increasing IgG N-glycosylation. These effects were dependent on the progesterone-induced blocking factor (PIBF), whose concentration was modulated by progesterone. PIBF was previously found to be an immunomodulatory molecule relevant for the maintenance of pregnancy. We concluded that the STT3-B/STT3-A ratio modulates the N-glycosylation level of IgG, in agreement with previous data showing that full N-glycosylation of polypeptides requires cooperation between both catalytic isoforms. This work provides the first evidence that STT3 isoforms can be hormonally modulated, with marked consequences on IgG N-glycosylation.

Original languageEnglish
Pages (from-to)28-37
Number of pages10
JournalImmunology Letters
Volume137
Issue number1-2
DOIs
Publication statusPublished - Jun 30 2011

Fingerprint

Glycosylation
Progesterone
Protein Isoforms
Immunoglobulin G
Polysaccharides
Pregnancy Maintenance
Peptides
Antibody Affinity
Hybridomas
Endoplasmic Reticulum
dolichyl-diphosphooligosaccharide - protein glycotransferase
Catalytic Domain
Cell Culture Techniques

Keywords

  • IgG
  • IL-6
  • N-glycosylation
  • PIBF
  • Progesterone
  • STT3

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Progesterone induces a switch in oligosaccharyltransferase isoform expression : Consequences on IgG N-glycosylation. / Prados, M. Belén; La Blunda, Julia; Szekeres-Barthó, J.; Caramelo, Julio; Miranda, Silvia.

In: Immunology Letters, Vol. 137, No. 1-2, 30.06.2011, p. 28-37.

Research output: Contribution to journalArticle

Prados, M. Belén ; La Blunda, Julia ; Szekeres-Barthó, J. ; Caramelo, Julio ; Miranda, Silvia. / Progesterone induces a switch in oligosaccharyltransferase isoform expression : Consequences on IgG N-glycosylation. In: Immunology Letters. 2011 ; Vol. 137, No. 1-2. pp. 28-37.
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