Recent high throughput sequencing analysis has revealed that the TCRβ repertoire is largely different between CD8+ and CD4+ T cells. Here, we show that the transduction of SIG35α, the public chain-centric HLA-A∗02:01(A2)/MART1 27-35 TCRα hemichain, conferred A2/MART1 27-35 reactivity to a substantial subset of both CD8+ and CD4+ T cells regardless of their HLA-A2 positivity. T cells individually reconstituted with SIG35α and different A2/MART1 27-35 TCRβ genes isolated from CD4+ or CD8+ T cells exhibited a wide range of avidity. Surprisingly, approximately half of the A2/MART1 27-35 TCRs derived from CD4+ T cells, but none from CD8+ T cells, were stained by A2/MART1 27-35 monomer and possessed broader cross-reactivity. Our results suggest that the differences in the primary structure of peripheral CD4+ and CD8+ TCRβ repertoire indeed result in the differences in their ability to form extraordinarily high avidity T cells which would otherwise have been deleted by central tolerance.
|Publication status||Published - 2016 Mar 31|
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