Humans lack iGb3 due to the absence of functional iGb3-synthase: Implications for NKT cell development and transplantation
2008

Humans Do Not Produce iGb3

publication Evidence: high

Author Information

Author(s): Christiansen Dale, Milland Julie, Mouhtouris Effie, Vaughan Hilary, Pellicci Daniel G, McConville Malcolm J, Godfrey Dale I, Sandrin Mauro S

Primary Institution: The University of Melbourne

Hypothesis

Do humans express a functional iGb3 synthase (iGb3S) responsible for lipid synthesis?

Conclusion

Humans lack functional iGb3 synthase, making iGb3 unlikely to be a natural ligand for NKT cells and posing risks in xenotransplantation.

Supporting Evidence

  • iGb3S mRNA was not detected in any human tissue analyzed.
  • Chimeric human iGb3S molecules were unable to synthesize iGb3.
  • Purified human anti-Gal antibodies bound to iGb3 lipid and mediated lysis of cells expressing iGb3.

Takeaway

Humans don't make a specific lipid called iGb3, which is important for certain immune cells. This could cause problems when using pig organs for transplants.

Methodology

The study involved analyzing human tissues for iGb3S mRNA and testing the functional activity of chimeric human iGb3S molecules.

Limitations

The study did not assess the presence of iGb3 at very low levels that might still be biologically significant.

Digital Object Identifier (DOI)

10.1371/journal.pbio.0060172

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