Defining the genetic determinants of T cell receptor repertoire at bulk and single-cell level
For our next talk, in the BDI/CHG (gen)omics Seminar series, we will be hearing from Yang Luo, Kennedy Trust for Rheumatology Research (KTRR) Senior Research Fellow in Data Science; Esther Ng, Senior Statistical Computational Bioscientist, Kennedy Institute of Rheumatology and Hannah Kockelbergh, Postdoctoral Researcher in Genomics, Kennedy Institute of Rheumatology. We’re delighted to host Yang, Esther and Hannah in what promises to be a great talk!

Date: Tuesday 18 February
Time: 9:30 am – 10:30 am
Talk title: Defining the genetic determinants of T cell receptor repertoire at bulk and single-cell level

Location: Big Data Institute, Seminar Room 0

Abstract
The interaction between Human Leukocyte Antigens (HLA) and T Cell Receptors (TCRs) is fundamental to the adaptive immune response, enabling the immune system to recognize and respond to pathogens while distinguishing self from non-self. In cancer immunotherapy, particularly in the context of immune checkpoint blockade (ICB) treatment, CD8+ T cells play a pivotal role, with their activity reliant on antigen recognition mediated by the TCR repertoire. Despite its importance, the contribution of genetic variation to TCR diversity and its impact on cancer treatment outcomes remains underexplored. In this study, we investigated the genetic determinants influencing the TCR repertoire, focusing on variable gene usage and CDR3 K-mer composition in pre- and post-ICB treatment samples. Furthermore, we extended our analysis to the single-cell level using data from the COVID-19 Multi-Omic Blood Atlas Consortium, uncovering cell-type-specific regulatory relationships between genetic variants and TCR repertoires.

Short bio
Luo lab develops statistical and computational methods for understanding the contribution of genetic variations to immune-mediated traits. We focus in particular on the major histocompatibility complex (MHC) region. The MHC region encodes proteins that play a vital role in our immune response. For a vast number of immune-mediated traits, MHC accounts for more genetic heritability than all other genomic variations combined. However, the exact molecular mechanisms behind MHC disease risk are yet unsolved. Knowledge of this would have an impact on subsequent cellular and clinical outcomes. We leverage large biobank data , gene expression data, and protein concentrations, to understand the precise biological mechanisms through which genetic variation is mediated to modulate risk of immune-mediated traits.

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All members of the University are welcome to join, please let reception at BDI know you’re here for the seminar and sign-in. We hope you can join us!

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As a reminder, the (gen)omics seminar series runs every other Tuesday morning and is intended to increase interaction between individuals working in genomics across Oxford. We encourage in-person attendance where possible. There is time for discussion over, tea, coffee and pastries after the talks.

Hybrid Option:
Please note that these meetings are closed meetings and only open to members of the University of Oxford to encourage sharing of new and unpublished data. Please respect our speakers and do not share the link with anyone outside of the university.

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Meeting ID: 313 061 637 884
Passcode: NG9dF3s8

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Date: 18 February 2025, 9:30
Venue: Big Data Institute, Old Road Campus OX3 7LF
Venue Details: Seminar room 0
Speaker: Various Speakers
Organising department: Big Data Institute (NDPH)
Organisers: Nicola Whiffin (University of Oxford), Duncan Palmer (University of Oxford)
Organiser contact email address: sumeeta.maheshwari@ndph.ox.ac.uk
Hosts: Nicola Whiffin (University of Oxford), Duncan Palmer (University of Oxford)
Part of: BDI/CHG Genomics Seminar Series
Booking required?: Not required
Audience: Members of the University only
Editor: Sumeeta Maheshwari