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HLA-DR and H-2E transgenes differentially mediate TCR-specific positive selection
J I Elliott1, K Takács, D M Altmann
1Transplantation Biology Section, Clinical Research Centre, Middlesex, UK.
International Immunology
|October 1, 1993
Summary
Human MHC molecules influence mouse T cell receptor (TCR) selection in transgenic models. Hybrid DR alpha/E beta complexes mediate TCR positive selection, but efficiency varies, suggesting peptide-dependent mechanisms.
Area of Science:
- Immunology
- Transgenic models
- T cell receptor repertoire
Background:
- Human MHC molecules are assumed to influence mouse TCR repertoire positive selection in disease models.
- Understanding this interaction is crucial for developing accurate transgenic models of human immunity.
Purpose of the Study:
- To compare the ability of DR alpha/E beta and E alpha/E beta complexes to induce TCR positive selection.
- To investigate the role of endogenous peptides in TCR selection by MHC molecules.
Main Methods:
- Utilized H-2Ea and HLA-DRA transgenic mice lacking endogenous E alpha.
- Assessed positive selection of specific T cell receptor V beta subsets (V beta 2, V beta 6, V beta 10).
Main Results:
- Both E alpha/E beta and DR alpha/E beta complexes mediated positive selection of V beta 2, V beta 6, and V beta 10 cells.
- Positive selection of V beta 10+ cells was less efficient in DRA transgenic mice compared to H-2Ea mice.
- Positive selection was not restricted to the CD4+ subset, occurring in CD4+, CD8+, or both subpopulations depending on the V beta specificity.
Conclusions:
- Differential binding of endogenous peptides to MHC complexes influences TCR positive selection.
- The selection process is complex and can affect distinct T cell subsets (CD4+ and CD8+).
- Findings provide insights into the mechanisms of TCR repertoire shaping by human MHC molecules in mice.