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Indirect allorecognition in solid organ transplantation.
P E Harris1, R Cortesini, N Suciu-Foca
1Department of Pathology, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
Reviews in Immunogenetics
|March 21, 2001
Summary
T cell recognition of donor antigens drives organ transplant rejection. Immune responses can broaden over time, increasing rejection risk and guiding new therapies.
Area of Science:
- Immunology
- Transplantation Science
- Cellular Biology
Background:
- Recipient T cell recognition of donor major histocompatibility complex (MHC) alloantigens is critical in organ transplant rejection.
- Two pathways exist: direct (intact MHC on donor antigen-presenting cells) and indirect (processed peptides on recipient antigen-presenting cells).
Purpose of the Study:
- To investigate the role of T cell recognition pathways in acute and chronic organ transplant rejection.
- To understand the evolution of T cell responses to alloantigens during the rejection process.
Main Methods:
- Analysis of recipient T cell responses to donor major histocompatibility complex (MHC) alloantigens.
- Examination of T cell reactivity patterns in primary acute and chronic organ transplant rejection.
Main Results:
- Initial T cell responses target a single dominant determinant on donor HLA-DR alloantigens.
- T cell reactivity expands to multiple epitopes and alloantigens in chronic rejection or recurrent episodes.
- Altered T cell allopeptide reactivity correlates with increased risk of rejection.
Conclusions:
- T cell recognition of alloantigens is a key driver of organ transplant rejection.
- The broadening of T cell responses over time is associated with heightened rejection risk.
- Findings support the development of novel therapeutic strategies and immunologic monitoring for transplant recipients.