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Updated: May 30, 2026
12:09
Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation
Published on: February 28, 2019
The link between major histocompatibility complex antibodies and cell proliferation.
Nicole M Valenzuela1, Elaine F Reed
1Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095-1652, USA.
Transplantation Reviews (Orlando, Fla.)
|August 2, 2011
Summary
Donor-specific antibodies targeting major histocompatibility complex (MHC) molecules directly promote transplant vasculopathy. These antibodies activate graft vascular cells, driving proliferation and inflammation, independent of complement or Fc receptors.
Area of Science:
- Transplantation immunology
- Vascular biology
- Immunopathology
Background:
- Transplant vasculopathy (TV) is a major cause of graft failure.
- Donor-specific antibodies (DSAs) targeting major histocompatibility complex (MHC) molecules are implicated in TV pathogenesis.
- The precise mechanisms by which DSAs induce TV remain under investigation.
Purpose of the Study:
- To review experimental evidence on the complement and Fc-independent effects of MHC class I and II antibodies on graft vascular cells.
- To elucidate the direct contribution of these antibody effects to the proliferative aspect of transplant vasculopathy.
Main Methods:
- Review of experimental literature on DSA effects on graft vasculature.
- Analysis of studies investigating antibody-mediated signaling pathways in endothelial and smooth muscle cells.
- Examination of evidence for complement and Fc-independent mechanisms.
Main Results:
- MHC class I and II DSAs directly activate proliferative, prosurvival, and migratory signaling in graft endothelial and smooth muscle cells.
- DSAs increase mitogenic factor expression in vascular endothelial cells, potentially creating autocrine loops.
- DSAs promote inflammatory cell recruitment, contributing to chronic inflammation, proliferation, and fibrosis.
Conclusions:
- MHC class I and II DSAs have direct, complement and Fc-independent effects on graft vascular cells.
- These effects contribute significantly to the proliferative pathology of transplant vasculopathy.
- Understanding these mechanisms is crucial for developing targeted therapies to prevent graft failure.
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