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High sequence homology between human and pig CD40 with conserved binding to human CD154
S A Rushworth1, C A Bravery, S Thompson
1Department of Surgery, University of Cambridge, United Kingdom.
Transplantation
|February 7, 2001
Summary
Human T cells may recognize pig CD40, a key molecule in immune responses. This interaction could impact pig-to-human xenograft survival by modulating immune cell functions.
Area of Science:
- Xenotransplantation immunology
- Molecular interactions in transplantation
- Immunogenicity of xenografts
Background:
- Pig-to-human xenograft survival depends on understanding molecular interactions between pig tissues and human immune cells.
- CD40 plays a crucial role in T cell interactions with antigen-presenting cells.
- Human T cells recognize pig MHC, and accessory molecules like CD28/B7 are compatible.
Purpose of the Study:
- To investigate the molecular compatibility of the CD40/CD154 pathway between humans and pigs.
- To assess the potential for human CD154 to bind to pig CD40.
- To evaluate the implications of these interactions for xenograft survival.
Main Methods:
- Cloning and sequencing of pig CD40.
- Detection of pig CD40 expression using flow cytometry with human CD154 (hCD154-Ig).
- Sequence comparison between human and pig CD40, and mutagenesis studies.
Main Results:
- Pig CD40 shares 74% amino acid identity with human CD40.
- Conserved residues essential for human CD40-CD154 binding are present in pig CD40.
- hCD154Ckappa bound to pig B cell lines and some human/pig lymphocytes, confirmed by transfected cell staining.
Conclusions:
- Human cells expressing CD154 can bind to donor pig CD40.
- These interactions may influence xenograft survival by modulating effector functions.
- Further research is needed to fully understand these interactions and their impact on xenograft outcomes.

