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A Method For Production of Recombinant mCD1d Protein in Insect Cells.
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Published on: December 10, 2007

Human CD1a deficiency is common and genetically regulated.

Chetan Seshadri1, Meera Shenoy, Richard D Wells

  • 1Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA 98195, USA. seshadri@u.washington.edu

Journal of Immunology (Baltimore, Md. : 1950)
|July 17, 2013
PubMed
Summary
This summary is machine-generated.

Common genetic variations significantly impact CD1a protein expression on dendritic cells (DCs). A specific SNP (rs366316) in the CD1a gene

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Area of Science:

  • Immunology
  • Genetics
  • Cell Biology

Background:

  • CD1 proteins present lipid antigens to T cells, but exhibit limited structural diversity.
  • The impact of genetic variations in regulatory regions on CD1 protein expression remains largely unexplored.
  • CD1a is a key isoform involved in lipid antigen presentation.

Purpose of the Study:

  • To investigate the diversity of inducible CD1a expression on human dendritic cells (DCs).
  • To determine the functional consequences of CD1a deficiency in DCs.
  • To identify genetic factors, specifically single nucleotide polymorphisms (SNPs), that regulate CD1a expression.

Main Methods:

  • Analysis of inducible CD1a expression patterns on human DCs.
  • Functional assays using CD1a-deficient DCs, including antigen presentation and response to LPS.
  • Genotyping for SNPs in regulatory regions and association studies with CD1a expression levels.
  • Reporter gene assays (promoter-luciferase system) to assess the functional impact of identified SNPs.

Main Results:

  • Significant, previously unappreciated diversity in inducible CD1a expression was observed on human DCs.
  • CD1a-deficient DCs showed impaired presentation of mycobacterial lipopeptide but retained other DC functions.
  • A common SNP (rs366316) in the 5' untranslated region was strongly associated with reduced CD1a surface expression and mRNA levels.
  • The polymorphic allele of rs366316 significantly decreased CD1a promoter activity by 44% in reporter assays.

Conclusions:

  • Inducible CD1a expression on DCs is genetically regulated by common SNPs in regulatory regions.
  • This genetic regulation provides a mechanism for population-level variation in immune responses to lipid antigens.
  • Despite limited structural diversity, CD1a-mediated immune responses can vary due to differences in gene expression levels.