CTLA-4 and autoimmune thyroid disease: Lack of influence of the A49G signal peptide polymorphism on functional recombinant human CTLA-4

Yang Xu, Peter N. Graves, Yaron Tomer, Terry F. Davies

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

A single nucleotide A49G polymorphism (SNP) of CTLA-4 has been linked and associated with the autoimmune thyroid diseases (AITD) and thyroid autoantibody secretion. We have explored the functional mechanisms of CTLA-4 by means of recombinant human CTLA-4 expressed on transfected Jurkat T cells. Analysis of CTLA-4 transcripts with quantitative real-time PCR demonstrated similar baseline and PHA-stimulated levels for both the A49 and G49 alleles, which were markedly enhanced by anti-CTLA-4 engagement. Both alleles also coded for proteins which were expressed on the cell membrane, as measured by FACS analysis using anti-CTLA-4 (G: 34.4 ± 11.9% cells, A: 27.6 ± 8.6% cells) (p = ns). Baseline and PHA-stimulated IL-2 production were also similar among control and CTLA-4 clones expressing both alleles. After anti-CTLA-4 engagement, IL-2 production was markedly inhibited in a dose- and time-dependent manner but this also appeared to be similar in the A and G allele expressing cells (95.7 ± 1.2% inhibition and 94.9 ± 1.1% inhibition, respectively). In conclusion, both the extrinsic and intrinsic actions of human CTLA-4 were not affected by the signal peptide A49G polymorphism. Therefore, the linkage of the CTLA-4 A49G SNP to AITD is most likely secondary to linkage disequilibrium.

Original languageEnglish (US)
Pages (from-to)133-140
Number of pages8
JournalCellular Immunology
Volume215
Issue number2
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Thyroid Diseases
Protein Sorting Signals
Autoimmune Diseases
Alleles
Interleukin-2
Single Nucleotide Polymorphism
Jurkat Cells
Linkage Disequilibrium
Autoantibodies
Real-Time Polymerase Chain Reaction
Thyroid Gland
Clone Cells
Cell Membrane
T-Lymphocytes
Proteins

Keywords

  • CTLA-4
  • IL-2
  • Jurkat T cells
  • SNP
  • Thyroid

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

Cite this

CTLA-4 and autoimmune thyroid disease : Lack of influence of the A49G signal peptide polymorphism on functional recombinant human CTLA-4. / Xu, Yang; Graves, Peter N.; Tomer, Yaron; Davies, Terry F.

In: Cellular Immunology, Vol. 215, No. 2, 2002, p. 133-140.

Research output: Contribution to journalArticle

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