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Analysis of the mechanisms that direct gamma-delta T cell homing and function.


The genes coding for the alpha, beta, gamma and delta T cell receptor (TCR) chains were cloned over 20 years ago. However, still relatively little is known about T cells that utilize the gamma-delta TCR. Particularly the biological functions of gamma-delta T cells and the mechanisms that govern their homing to specific epithelial tissues remain enigmatic.

In the blood and in secondary lymphoid organs, only 1% to 3 % of the T cells are gamma-delta T cells. In contrast, gamma-delta T cells are disproportionately enriched in various epithelial tissues, where they often constitute the majority of the intraepithelial lymphocytes (IELs).

Specific subsets of gamma-delta T cells with tissue-specific semi-invariant TCR repertoires reside in the epithelia of the skin, the small intestine, the vagina/reproductive tract, the decidua, the lung/respiratory tract, and in the nasal mucosa. In the proposed work we will investigate the function and tissue homing properties of the TCR gamma-delta + IELs found in various epithelial tissues.

To date, such analysis is hampered by two circumstances:
- First, the only gamma-delta T cell specific marker in the human or mouse system is the gamma-delta TCR itself. Therefore, detection of gamma-delta T cells with monoclonal antibodies (mAb) specific gamma-delta TCR for their will activate the cells and will obstruct further analysis.
- Second, activated gamma-delta T cells often down-regulate their TCR to non-detectable levels. To circumvent these obstacles, I have developed, during my Marie Curie fellowship in the laboratory of Dr.Bernard Malissen, a novel targeting approach that allows the direct identification of gamma-delta T cells in vivo without prior manipulation (Prinz et al., 2006, Nature Immunology, in press). I will use this model during the reintegration period to investigate the mechanisms that direct gamma-delta T cell homing and function.

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Carl-neuberg Str. 1