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• W3200479278 abstract "Competition between antigen-specific T cells for peptide:MHC (p:MHC) complexes shapes the ensuing T cell response. Mouse model studies provided compelling evidence that competition is a highly effective mechanism controlling the activation of naive T cells. However, assessing the effect of T cell competition in the context of a human infection requires defined pathogen kinetics and trackable naive and memory T cell populations of defined specificity. A unique cohort of non-myeloablative hematopoietic stem cell transplant (nmHSCT) patients allowed us to assess T cell competition in response to CMV reactivation, which was documented with detailed virology data. In our cohort, HSCT donors and recipients were CMV-seronegative and -positive, respectively, thus providing genetically distinct memory and naive T cell populations. We used single-cell transcriptomics to track donor versus recipient-derived T cell clones over the course of 90 days. We found that donor-derived T cell clones proliferated and expanded substantially following CMV-reactivation. However, for immunodominant CMV epitopes, recipient-derived memory T cells remained the overall dominant population. This dominance was maintained despite more robust clonal expansion of donor-derived T cells in response to CMV reactivation. Interestingly, the donor-derived T cells that were recruited into these immunodominant memory populations shared strikingly similar TCR properties with the recipient-derived memory T cells. This selective recruitment of identical and nearly identical clones from the naive into the immunodominant memory T cell pool suggests that competition does not interfere with rejuvenating a memory T cell population, but results in selection of convergent clones to the memory T cell pool." @default.
• W3200479278 created "2021-09-27" @default.
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• W3200479278 date "2021-09-15" @default.
• W3200479278 modified "2023-10-15" @default.
• W3200479278 title "Convergent clonal selection of donor- and recipient-derived CMV-specific T cells in hematopoietic stem cell transplant patients" @default.
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• W3200479278 doi "https://doi.org/10.1101/2021.09.14.458942" @default.
• W3200479278 hasPublicationYear "2021" @default.
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