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Pre–T cell receptors topologically sample self-ligands during thymocyte β-selection

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Science  08 Jan 2021:
Vol. 371, Issue 6525, pp. 181-185
DOI: 10.1126/science.abe0918

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PreTCRs use horizontal docking geometry

The T cell receptor (TCR) recognizes peptide-bound major histocompatibility complex molecules (pMHCs) and consists of an α chain in association with a β chain. Both chains have hypervariable complementarity-determining regions (CDRs) that inform whether a particular TCR can recognize a given pMHC. To successfully graduate from the thymus, aspiring αβT cells must generate a functional TCR. During one early checkpoint in this process, the β chain is first paired with a preTβ chain to form the preTCR. Li et al. used x-ray crystallography to visualize how preTCRs recognize pMHCs. They report that the CDR3 loop of the preTCR β chain contacts the pMHC with a distinctive lateral topography. This is in contrast to the established binding modality of mature TCRs, whereby all three CDR loops on both α and β chains bind in a vertical orientation. These complexes help solve the mystery of how only functionally rearranged β chains using competent CDR3 loops can properly engage with pMHC at the preTCR stage.

Science, this issue p. 181

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