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CD4(+) and CD8(+) TCR? repertoires possess different potentials to generate extraordinarily high-avidity T cells.


ABSTRACT: Recent high throughput sequencing analysis has revealed that the TCR? repertoire is largely different between CD8(+) and CD4(+) T cells. Here, we show that the transduction of SIG35?, the public chain-centric HLA-A*02:01(A2)/MART127-35 TCR? hemichain, conferred A2/MART127-35 reactivity to a substantial subset of both CD8(+) and CD4(+) T cells regardless of their HLA-A2 positivity. T cells individually reconstituted with SIG35? and different A2/MART127-35 TCR? genes isolated from CD4(+) or CD8(+) T cells exhibited a wide range of avidity. Surprisingly, approximately half of the A2/MART127-35 TCRs derived from CD4(+) T cells, but none from CD8(+) T cells, were stained by A2/MART127-35 monomer and possessed broader cross-reactivity. Our results suggest that the differences in the primary structure of peripheral CD4(+) and CD8(+) TCR? 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.

PROVIDER: S-EPMC4814874 | BioStudies | 2016-01-01T00:00:00Z

REPOSITORIES: biostudies

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