Individual TCR ? and ? genes are rearranged and expressed in a series of overlapping waves during murine development with cells bearing specific TCR preferentially or exclusively migrating from the thymus to specific epithelial and lymphoid sites. ?? T cells that rearrange their TCR during early fetal development express highly restricted or invariant TCR. The first TCR-bearing cells migrate from the developing thymus to the skin where they take up residence in the epidermis as Thy-1+ dendritic epidermal T cells (DETC). Similarly, subsequent waves of ?? TCR expressing thymocytes migrate to other epithelial tissues. The presence of these ?? T cell populations with restricted TCR use in distinct epithelial locations supports recognition of unique, tissue- specific antigens and specialized functions for these cells. However, roles for TCR signals in development and ligands for these invariant ?? TCRs are currently poorly understood. We hypothesize that novel endogenous V?3V?1 TCR ligands are expressed in the embryonic thymus and deliver key signals for DETC precursor development and that expression of these ligands is upregulated on skin epithelial cells following stress and functions to deliver activation signals to DETC following injury or stress. We have developed tools for detection of V?3V?1 TCR ligands and found expression on embryonic, but not adult, thymic epithelial cells. Based upon these results, we are now in a position to identify and characterize this fetal TCR ligand and determine its role in DETC precursor development and activation of DETC function.
?? T cells reside in epithelial barrier tissues where they form a first line of defense against environmental assaults and play roles in wound healing and tumor killing. Identification of T cell receptor ligands that play roles in their development and function is essential for utilization of these cells in therapeutic approaches to improve wound healing and eradicate skin tumors.
|Nielsen, Morten M; Witherden, Deborah A; Havran, Wendy L (2017) ?? T cells in homeostasis and host defence of epithelial barrier tissues. Nat Rev Immunol 17:733-745|