T-CELLS WITH DUAL ANTIGEN-SPECIFICITY IN T-CELL RECEPTOR TRANSGENIC MICE REJECTING ALLOGRAFTS

Allelic exclusion of T cell receptor (TCR) genes is incomplete: a sign ificant percentage (10-30 %) of normal human and mouse peripheral T ce lls express two surface TCR alpha chains, and a small percentage of pe ripheral human T cells have been reported to express two surface TCR b eta chains. A proportion of thymocytes in TCR transgenic mice rearrang e endogenous T cell receptor genes, and peripheral T cells with two TC R alpha chains, transgenic and endogenous, have been reported. T cell clones with more than a single TCR heterodimer on their surface might be expected to show specificity for more than one cognate antigen: we report here a T cell clone with dual antigen specificity, isolated fro m an F5 TCR influenza nucleoprotein (NP 366-374/D-b)-specific transgen ic female mouse which had rejected an H-2-matched male skin graft. It was selected in vitro by stimulation with male H-2(b) spleen cells in the absence of the NP366-374 peptide but has specificity for both H-Y/ D-b and NP366-374. This contrasted with the single NP366-374/D-b speci ficity shown by a control clone isolated from a Rag1-/- F5 mouse. The dual antigen specificity was associated with the rearrangement of endo genous TCR genes and cell surface expression of these as well as the T CR transgene.