Understanding the Immune Response to Carbohydrate Xenoantigens
Author Information
Author(s): Kearns-Jonker Mary, Barteneva Natasha, Mencel Robert, Hussain Namath, Shulkin Irina, Xu Alan, Yew Margaret, Cramer Donald V
Primary Institution: Saban Research Institute of the Children's Hospital of Los Angeles, University of Southern California Keck School of Medicine
Hypothesis
A unique structural configuration defines IgM and IgG xenoantibodies directed at pig cells and/or xenografts in the presence or absence of somatic mutation.
Conclusion
Xenoantibodies induced during early and delayed xenograft responses are predominantly encoded by genes in the VH3 family, with a small proportion encoded by VH4 germline progenitors.
Supporting Evidence
- Natural antibodies directed at carbohydrates reject porcine xenografts.
- The VH4-59 gene encodes antibodies in the VH4 family that are induced in human patients.
- Key contact sites for xenoantibody/carbohydrate interaction include specific amino acids in the IgVH gene.
- Site-directed mutagenesis indicates that mutations in predicted contact sites alter binding to carbohydrate xenoantigens.
- Computer-simulated models depict the structure of xenoantibodies with accuracy.
Takeaway
This study looks at how certain antibodies in our body react to pig organs, helping us understand how to make organ transplants safer.
Methodology
The study involved sequencing immunoglobulin genes from patients and non-human primates, creating cDNA libraries, and using computer-simulated modeling to analyze antibody structures.
Limitations
Limited information on light chain genes and the specific role of VH4-59 germline progenitor xenoantibodies.
Participant Demographics
Patients and non-human primates exposed to porcine cells.
Digital Object Identifier (DOI)
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