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The CDR3delta repertoire of gamma/delta T cells from blood donors infected with Neoehrlichia. mikurensis
University of Skövde, School of Bioscience.
2025 (English)Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
Abstract [en]

N. mikurensis is a tick-borne bacterial pathogen that causes a severe infection called neoehrlichiosis. Symptoms can range from mild (e.g., headaches and fever) to severe (e.g., vascular and thromboembolic events). N. mikurensis often presents as a fever of unknown origin in immunocompromised patients. Individuals undergoing treatment for lymphoma who were infected with N. mikurensis showed an elevated clonal count of perforin-producing γδ T cells. To gain insight into T cell receptor (TCR) characteristics associated with this pathogen, TCR repertoire analysis was conducted on healthy, asymptomatic blood donors. The analysis compared N. mikurensis-infected individuals (n = 11; 3900 CDR3δ) with uninfected individuals (n = 11; 4299 CDR3δ). The full repertoire analysis included CDR3δ length, as well as N-addition length analysis between infected and uninfected blood donors. Diversity metrics based on clonotype richness, Shannon entropy and Simpson’s diversity, as well as overlap comparisons, were carried out to identify unique CDR3δ that link exclusively to infected individuals. PCA using FASGAI descriptors was generated for the CDR3δ to connect amino acid physicochemical properties with antigen-specificity and binding to N. mikurensis. Public CDR3δ identified in infected samples were also compared with public databases of fetal repertoires to classify the origin of N. mikuresis-infected CDR3δs. Full CDR3δ length and N-addition length showed significant differences, highlighting decreased clonotype frequency in infected samples. Meanwhile, diversity and PCA remained the same between both groups. The overlap revealed 7 public CDR3δ CDR3δ that were unique to N. mikurensis-infected samples. These CDR3δ were shown to have shorter CDR3δ lengths and considerably fewer N-additions at the VD- and DJjunctions. The fetal comparison to both the uninfected and infected groups exhibited similar diversity, but distinct physicochemical properties, with CDR3δ displaying an average bias toward specific FASGAI descriptors. There was greater overlap between fetal-derived CDR3δ and those from infected individuals than with the uninfected group. 34 public CDR3δ were shared with the infected group. These fetal-derived CDR3δ exhibited more distinct V(D)J rearrangements and consisted of not only TRDJ1 gene segments, as expected based on the total repertoire results, but also a similar number of TRDJ3 segments. Notably, there were few N-additions. In summary, a higher numbers of public CDR3δ CDR3δ in the N. mikurensis-infected samples were found than in uninfected samples. Due to their innate characteristics, these CDR3δ were likely of fetal origin. Further testing is needed to determine whether they are involved in the immune defense against N. mikurensis

Place, publisher, year, edition, pages
2025. , p. 37
National Category
Medical Bioinformatics and Systems Biology
Identifiers
URN: urn:nbn:se:his:diva-25714OAI: oai:DiVA.org:his-25714DiVA, id: diva2:1988275
External cooperation
Göteborgs Universitet
Subject / course
Systems Biology
Educational program
Molecular Biotechnology - Master's Programme, 120 ECTS
Supervisors
Examiners
Available from: 2025-08-11 Created: 2025-08-11 Last updated: 2025-09-29Bibliographically approved

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CiteExportLink to record
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