{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:56:25Z","timestamp":1753890985526,"version":"3.41.2"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T00:00:00Z","timestamp":1642464000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"Background<\/jats:title>The T cell receptor (TCR) diversity is essential for effective T cell immunity. Previous studies showed that TCR diversity in Wiskott\u2013Aldrich Syndrome (WAS) patients was severely impaired, especially in the memory T cell populations. Whether this defect was caused by intrinsic WASp deficiency or extrinsic reasons is still unclear.<\/jats:p><\/jats:sec>Methods<\/jats:title>We sorted different T cell subsets from the bone marrow chimeric mice model using both magnetic beads and flow cytometry. TCR repertoires of memory T cells, especially CD4+<\/jats:sup> effector memory T (TEM) cells and CD8+<\/jats:sup> central memory T (TCM) cells, were analyzed using the UMI quantitative high-throughput sequencing (HTS).<\/jats:p><\/jats:sec>Results<\/jats:title>An average of 5.51 million sequencing reads of 32 samples was obtained from the Illumina sequencing platform. Bioinformatic analyses showed that compared with wild type (WT), WAS knock out (KO)-CD4+<\/jats:sup> TEM cells exhibited increased Simpson index and decreased D50 index (P &lt;0.05); The rank abundance curve of KO-CD4+<\/jats:sup> TEM cells was shorter and steeper than that of WT, and the angle of q<\/jats:sup>D and q in KO-CD4+<\/jats:sup> TEM cells was lower than that of WT, while these indexes showed few changes between WT and KO chimeric mice in the CD8+<\/jats:sup>TCM population. Therefore, it indicated that the restriction on the TCRV\u03b2 repertoires is majorly in KO-CD4+<\/jats:sup> TEM cells but not KO- CD8+<\/jats:sup> TCM cells. Principal Component Analysis (PCA), a comprehensive parameter for TCRV\u03b2 diversity, successfully segregated CD4+<\/jats:sup> TEM cells from WT and KO, but failed in CD8+<\/jats:sup> TCM cells. Among the total sequences of TRB<\/jats:italic>, the usage of TRBV12.2, TRBV30, TRBV31, TRBV4, TRBD1, TRBD2, TRBJ1.1, and TRBJ1.4 showed a significant difference between WT-CD4+<\/jats:sup> TEM cells and KO-CD4+<\/jats:sup> TEM cells (P &lt;0.05), while in CD8+<\/jats:sup> TCM cells, only the usage of TRBV12.2 and TRBV20 showed a substantial difference between WT and KO (P &lt;0.05). No significant differences in the hydrophobicity and sequence length of TCRV\u03b2 were found between the WT and KO groups.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>WASp deficiency selectively affected the TCR diversity of different memory T cell subsets, and it had more impact on the TCRV\u03b2 diversity of CD4+<\/jats:sup> TEM cells than CD8+<\/jats:sup> TCM cells. Moreover, the limitation of TCRV\u03b2 diversity of CD4+<\/jats:sup> TEM cells and CD8+<\/jats:sup> TCM cells in WAS was not severe but intrinsic.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2021.794795","type":"journal-article","created":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T04:43:37Z","timestamp":1642481017000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["WASp Deficiency Selectively Affects the TCR Diversity of Different Memory T Cell Subsets in WAS Chimeric 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