Due to copyright issues, an electronic copy of the thesis must be ordered from the faculty. For the faculty to have time to process the order, the order must be received by the faculty at the latest 2 days before the public defence. Orders received later than 2 days before the defence will not be processed. After the public defence, please address any inquiries regarding the thesis to the candidate.
Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Associate Professor Rachael Bashford-Rogers, University of Oxford, UK
- Second opponent: Adjunct Professor Päivi Saavalainen, University of Helsinki, Finland
- Third member and chair of the evaluation committee: Professor Dag Undlien, University of Oslo
Chair of the Defence
Professor Tom Hemming Karlsen, University of Oslo
Principal Supervisor
Professor Ludvig Sollid, University of Oslo
Summary
Adaptive immunity relies on the diverse repertoires of B cell and T cell receptors (BCRs and TCRs) which are generated through V(D)J recombination and also shaped by germline genetic variation. Inherited polymorphisms and structural variants within immunoglobulin (IG) and TCR loci influence receptor gene usage and contribute substantially to inter-individual repertoire variation. Coeliac disease (CeD), a genetically well-characterised immune-mediated disorder strongly associated with HLA class II allotypes (particularly HLA-DQ2.5), provides a model to investigate how these inherited effects shape disease-relevant immune repertoires.
In this thesis work, sequencing of naïve BCR and TCR repertoires from approximately 100 individuals with CeD and 100 controls was integrated with dense genotyping to characterise genetic influences on the naïve repertoire. Widespread cis-acting associations between germline variants and IG gene usage were identified across heavy and light chain loci. However, no CeD-specific differences in naïve BCR gene usage were observed. By contrast, naïve CD4+ TCR gene usage showed a more complex architecture, shaped by both cis-acting variants and strong trans-acting effects from the HLA region. HLA-DQ2.5 was associated with increased usage of TCR V genes linked to gluten reactivity, explaining the higher usage observed in CeD. Machine learning analyses confirmed that TCR repertoire-based classification was driven primarily by HLA rather than disease status. Overall, this work demonstrates that germline genetic variation – particularly HLA – influences the composition of naïve adaptive immune receptor repertoires.
Additional information
Contact the research support staff.