AIRR-C Seminar Series, November 30, 2023 - Aaron Michels, CU Anschutz Medical Campus, USA
802 بار بازدید -
7 ماه پیش
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Temporal Development of T cell
Temporal Development of T cell receptor Repertoires during Childhood in Health and Type 1 Diabetes
Established Speaker: Aaron Michels, University of Colorado Anschutz Medical Campus, USA
Talk abstract
T cells targeting self-proteins are important mediators in autoimmune diseases such as type 1 diabetes (T1D). T cells express unique cell-surface receptors (TCRs) which recognize peptides presented by major histocompatibility molecules. Here, we deep-sequenced the TCR beta chain (TCRβ) repertoires from longitudinal peripheral blood DNA samples at four time points beginning early in life from children that progressed to clinical T1D (n=29) and age/sex/HLA-matched pancreatic islet autoantibody negative controls (n=25). From 53 million TCRβ sequences, we show that the TCRβ repertoire is extraordinarily diverse early in life and narrows with age independent of disease. We demonstrate the ability to identify and track shared antigen-specific TCRβ sequences, those responding to viral peptides and separately islet proteins. Public islet antigen-specific TCRβ sequences had different patterns of accumulation based upon self-antigen specificity in the preclinical T1D cases (e.g., those responding to insulin, glutamic acid decarboxylase, or zinc transporter 8). As an independent validation, we sequenced and analyzed TCRβ repertoires from a cohort of newly diagnosed T1D patients (n=143), identifying the same islet-antigen reactive TCRs. Furthermore, 73 public islet-antigen TCRβ sequences were present in higher frequencies and numbers in T1D samples compared to controls. The total number of these disease-relevant TCRβ sequences inversely correlated with age at clinical diabetes diagnosis, highlighting the importance of using disease-relevant TCR sequences as powerful biomarkers in autoimmune disorders.
Speaker Bio
Aaron Michels MD, is a physician-scientist at the Barbara Davis Center for Diabetes, which is part of the University of Colorado. He has lived with type 1 diabetes for more than three decades and is committed to caring for patients with diabetes along with conducting research to prevent and ultimately cure the disease. His research focuses on understanding the basic immunology of type 1 diabetes to monitor diabetes-specific T cell receptor sequences during the stages of type 1 diabetes development and design safe and specific therapies to stop the autoimmune destruction of insulin producing pancreatic beta cells.
http://www.michelslab.com/
AIRR-C Seminar Series website: https://www.antibodysociety.org/the-a...
Established Speaker: Aaron Michels, University of Colorado Anschutz Medical Campus, USA
Talk abstract
T cells targeting self-proteins are important mediators in autoimmune diseases such as type 1 diabetes (T1D). T cells express unique cell-surface receptors (TCRs) which recognize peptides presented by major histocompatibility molecules. Here, we deep-sequenced the TCR beta chain (TCRβ) repertoires from longitudinal peripheral blood DNA samples at four time points beginning early in life from children that progressed to clinical T1D (n=29) and age/sex/HLA-matched pancreatic islet autoantibody negative controls (n=25). From 53 million TCRβ sequences, we show that the TCRβ repertoire is extraordinarily diverse early in life and narrows with age independent of disease. We demonstrate the ability to identify and track shared antigen-specific TCRβ sequences, those responding to viral peptides and separately islet proteins. Public islet antigen-specific TCRβ sequences had different patterns of accumulation based upon self-antigen specificity in the preclinical T1D cases (e.g., those responding to insulin, glutamic acid decarboxylase, or zinc transporter 8). As an independent validation, we sequenced and analyzed TCRβ repertoires from a cohort of newly diagnosed T1D patients (n=143), identifying the same islet-antigen reactive TCRs. Furthermore, 73 public islet-antigen TCRβ sequences were present in higher frequencies and numbers in T1D samples compared to controls. The total number of these disease-relevant TCRβ sequences inversely correlated with age at clinical diabetes diagnosis, highlighting the importance of using disease-relevant TCR sequences as powerful biomarkers in autoimmune disorders.
Speaker Bio
Aaron Michels MD, is a physician-scientist at the Barbara Davis Center for Diabetes, which is part of the University of Colorado. He has lived with type 1 diabetes for more than three decades and is committed to caring for patients with diabetes along with conducting research to prevent and ultimately cure the disease. His research focuses on understanding the basic immunology of type 1 diabetes to monitor diabetes-specific T cell receptor sequences during the stages of type 1 diabetes development and design safe and specific therapies to stop the autoimmune destruction of insulin producing pancreatic beta cells.
http://www.michelslab.com/
AIRR-C Seminar Series website: https://www.antibodysociety.org/the-a...
7 ماه پیش
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