Related Experiment Videos
Contribution of direct and indirect recognition pathways to T cell alloreactivity
1Department of Pathology, College of Physicians and Surgeons of Columbia University, New York, New York 10032.
The Journal of Experimental Medicine
|June 1, 1993
Summary
This study shows that processed donor HLA molecules (allopeptides) presented by host cells trigger T cell responses. This indirect allorecognition, though less frequent than direct recognition, is crucial in chronic allograft rejection.
Area of Science:
- Immunology
- Transplantation immunology
Background:
- Allorecognition is critical in transplantation, involving direct and indirect pathways.
- The indirect pathway involves host antigen-presenting cells (APCs) processing donor antigens.
Purpose of the Study:
- To investigate T cell responses to allopeptides derived from HLA-DR molecules.
- To compare the frequency and significance of indirect allorecognition in T cell activation.
Main Methods:
- Mixed lymphocyte culture (MLC) using HLA-DR11/DR12 responders and DR1 stimulators.
- T cell proliferation assays and epitope mapping.
- Analysis of T cell receptor (TCR) V beta usage.
Main Results:
- Primed T cells proliferated to both intact DR1 cells and a DR1-derived peptide presented by host APCs.
- The dominant epitope was recognized when presented by the responder's HLA-DR12.
- T cells recognizing the DR1 peptide expressed TCR V beta 3.
- Indirect allorecognition T cell frequency was ~100-fold lower than direct recognition.
Conclusions:
- Alloreactivity is triggered by allopeptides processed and presented by host APCs.
- Indirect allorecognition, while less frequent, is significant in chronic allograft rejection.
- This pathway involves T helper cell activation and alloantibody production.