ORCID Profile
0000-0002-9570-2755
Current Organisation
Fred Hutchinson Cancer Research Center
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Publisher: American Association for the Advancement of Science (AAAS)
Date: 09-2010
DOI: 10.1126/SCITRANSLMED.3001442
Abstract: Deep sequencing of the T cell receptor repertoires of seven healthy adults reveals that the adaptive immune system is far less erse than expected and the person-to-person overlap is thousands of times larger.
Publisher: The American Association of Immunologists
Date: 15-01-2019
Abstract: With age, the immune system becomes less effective, causing increased susceptibility to infection. Chronic CMV infection further impairs immune function and is associated with increased mortality in the elderly. CMV exposure elicits massive CD8+ T cell clonal expansions and diminishes the cytotoxic T cell response to subsequent infections, leading to the hypothesis that to maintain homeostasis, T cell clones are expelled from the repertoire, reducing T cell repertoire ersity and diminishing the ability to combat new infections. However, in humans, the impact of CMV infection on the structure and ersity of the underlying T cell repertoire remains uncharacterized. Using TCR β-chain immunosequencing, we observed that the proportion of the peripheral blood T cell repertoire composed of the most numerous 0.1% of clones is larger in the CMV seropositive and gradually increases with age. We found that the T cell repertoire in the elderly grows to accommodate CMV-driven clonal expansions while preserving its underlying ersity and clonal structure. Our observations suggest that the maintenance of large CMV-reactive T cell clones throughout life does not compromise the underlying repertoire. Alternatively, we propose that the diminished immunity in elderly in iduals with CMV is due to alterations in cellular function rather than a reduction in CD8+ T cell repertoire ersity.
Publisher: American Society of Hematology
Date: 05-11-2009
DOI: 10.1182/BLOOD-2009-04-217604
Abstract: The adaptive immune system uses several strategies to generate a repertoire of T- and B-cell antigen receptors with sufficient ersity to recognize the universe of potential pathogens. In αβ T cells, which primarily recognize peptide antigens presented by major histocompatibility complex molecules, most of this receptor ersity is contained within the third complementarity-determining region (CDR3) of the T-cell receptor (TCR) α and β chains. Although it has been estimated that the adaptive immune system can generate up to 1016 distinct αβ pairs, direct assessment of TCR CDR3 ersity has not proved amenable to standard capillary electrophoresis-based DNA sequencing. We developed a novel experimental and computational approach to measure TCR CDR3 ersity based on single-molecule DNA sequencing, and used this approach to determine the CDR3 sequence in millions of rearranged TCRβ genes from T cells of 2 adults. We find that total TCRβ receptor ersity is at least 4-fold higher than previous estimates, and the ersity in the subset of CD45RO+ antigen-experienced αβ T cells is at least 10-fold higher than previous estimates. These methods should prove valuable for assessment of αβ T-cell repertoire ersity after hematopoietic cell transplantation, in states of congenital or acquired immunodeficiency, and during normal aging.
Publisher: Wiley
Date: 21-05-2019
DOI: 10.1002/AJH.25505
Location: United States of America
No related grants have been discovered for Edus Warren.