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Unexpected T-cell diversity in syngeneic graft-versus-host disease revealed by interaction with peptide-loaded soluble MHC class II molecules1
- Source :
- Transplantation. 75:1361-1367
- Publication Year :
- 2003
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2003.
-
Abstract
- BACKGROUND Administration of cyclosporine after syngeneic bone marrow transplantation elicits a systemic autoaggression syndrome termed syngeneic graft-versus-host disease (SGVHD). The effector T cells recognize a peptide from the invariant chain termed CLIP (MHC class II invariant chain peptide) presented on MHC class II molecules. Moreover, the N-terminal flanking region of CLIP interacts with the T-cell receptor (TcR) beta chain. METHODS The current study uses a novel approach to isolate and examine the responding T cells ex vivo. A soluble MHC class II molecule using immunoglobulin (Ig)G (MHC class II-Ig) as a scaffold was constructed. The MHC class II-Ig molecule loaded with different peptide variants of CLIP (lacking the N-terminal or C-terminal flanking regions of CLIP) was used to isolate antigen-specific T cells from animals with SGVHD by panning or by flow cytometric sorting. RESULTS Two subsets of antigen specific T cells restricted by the N- and C-terminal flanking regions of CLIP can be isolated during acute SGVHD that express the Vbeta8.5 TcR determinant but secrete different cytokines (interferon [IFN]-gamma, interleukin [IL]-10) as detected by real-time quantitative polymerase chain reaction (PCR). Spectratyping of the complementarity-determining region 3 regions reveals that the N-terminal CLIP reactive population has greater diversity in both the CDR3 and J regions than the C-terminal CLIP reactive subset. Interestingly, the N-terminal CLIP reactive cells can be preferentially detected in the target tissues during acute SGVHD. However, only IFN-gamma messenger (m)RNA was detected in the tissues. CONCLUSION The ability to isolate and examine antigen specific T cells ex vivo has revealed unexpected differences in TcR diversity and cytokine production in SGVHD.
Details
- ISSN :
- 00411337
- Volume :
- 75
- Database :
- OpenAIRE
- Journal :
- Transplantation
- Accession number :
- edsair.doi...........85e94dfd9b3e2b83a4a76cef145ebcdb
- Full Text :
- https://doi.org/10.1097/01.tp.0000063691.54928.cf