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Detection of Cell Surface Ligands for the TCR Using Soluble TCRs¹

Integrated Department of Immunology, National Jewish Medical and Research Center, Denver, CO 80206; and University of Colorado Health Sciences Center, Denver, CO 80262

The natural ligands recognized by TCRs are still largely unknown, in part because immunization does not normally result in Ag-specific T cell responses. Taking advantage of an established ligand for a particular TCR, we demonstrated that a multimerized recombinant form of this TCR can be used like a mAb to specifically detect its own ligand. Using the same approach for more common TCRs whose ligands remain unknown, we detected on certain cell lines molecules that appear to be ligands for three additional TCRs. One of these represents the mouse V6/V1 invariant TCR, which predominates in the female reproductive tract, the tongue, and the lung, and other tissues during inflammation. The second represents the closely related V5/V1 invariant TCR expressed by most epidermal T cells. The third is a V1/V6.3 TCR, representative of a variable type frequently found on lymphoid T cells. We found evidence that ligands for multiple TCRs may be simultaneously expressed on a single cell line, and that at least some of the putative ligands are protease sensitive. This study suggests that soluble versions of TCRs can be as tools to identify and characterize the natural ligands of T cells.

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