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Deep sequencing of the human TCR? and TCR? repertoires suggests that TCR? rearranges after ?? and ?? T cell commitment.
Sci Transl Med. 2011 Jul 6;3(90):90ra61
Authors: Sherwood AM, Desmarais C, Livingston RJ, Andriesen J, Haussler M, Carlson CS, Robins H
Abstract
T lymphocytes respond to a broad array of pathogens with the combinatorial diversity of the T cell receptor (TCR). This adaptive response is possible because of the unique structure of the TCR, which is composed of two chains, either ?? or ??, that undergo genetic rearrangement in the thymus. ?? and ?? T cells are functionally distinct within the host but are derived from a common multipotent precursor. The canonical model for T cell lineage commitment assumes that the ?, ?, and ? chains rearrange before ?? or ?? T cell commitment. To test the standard model in humans, we used high-throughput sequencing to catalog millions of TCR? and TCR? chains from peripheral blood ?? and ?? T cells from three unrelated individuals. Almost all sampled ?? and ?? T cells had rearranged TCR? sequences. Although sampled ?? T cells had a diverse repertoire of rearranged TCR? chains, less than 4% of ?? T cells in peripheral blood had a rearranged TCR? chain. Our data suggest that TCR? rearranges in all T lymphocytes, consistent with TCR? rearranging before T cell lineage commitment. However, rearrangement of the TCR? locus appears to be restricted after T cell precursors commit to the ?? T cell lineage. Indeed, in T cell leukemias and lymphomas, TCR? is almost always rearranged and TCR? is only rearranged in a subset of cancers. Because high-throughput sequencing of TCRs is translated into the clinic for monitoring minimal residual for leukemia/lymphoma, our data suggest the sequencing target should be TCR?.
PMID: 21734177 [PubMed - indexed for MEDLINE]
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Deep sequencing of the human TCR? and TCR? repertoires suggests that TCR? rearranges after ?? and ?? T cell commitment.
Sci Transl Med. 2011 Jul 6;3(90):90ra61
Authors: Sherwood AM, Desmarais C, Livingston RJ, Andriesen J, Haussler M, Carlson CS, Robins H
Abstract
T lymphocytes respond to a broad array of pathogens with the combinatorial diversity of the T cell receptor (TCR). This adaptive response is possible because of the unique structure of the TCR, which is composed of two chains, either ?? or ??, that undergo genetic rearrangement in the thymus. ?? and ?? T cells are functionally distinct within the host but are derived from a common multipotent precursor. The canonical model for T cell lineage commitment assumes that the ?, ?, and ? chains rearrange before ?? or ?? T cell commitment. To test the standard model in humans, we used high-throughput sequencing to catalog millions of TCR? and TCR? chains from peripheral blood ?? and ?? T cells from three unrelated individuals. Almost all sampled ?? and ?? T cells had rearranged TCR? sequences. Although sampled ?? T cells had a diverse repertoire of rearranged TCR? chains, less than 4% of ?? T cells in peripheral blood had a rearranged TCR? chain. Our data suggest that TCR? rearranges in all T lymphocytes, consistent with TCR? rearranging before T cell lineage commitment. However, rearrangement of the TCR? locus appears to be restricted after T cell precursors commit to the ?? T cell lineage. Indeed, in T cell leukemias and lymphomas, TCR? is almost always rearranged and TCR? is only rearranged in a subset of cancers. Because high-throughput sequencing of TCRs is translated into the clinic for monitoring minimal residual for leukemia/lymphoma, our data suggest the sequencing target should be TCR?.
PMID: 21734177 [PubMed - indexed for MEDLINE]
More...