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Title: Selection of the human cytomegalovirus specific CD8+ T cell repertoire following primary infection
Author: Day, E. K.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2006
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This study aimed to establish if the memory response observed in long-term HCMV carriers directly reflects the breadth of the T cell response generated following primary infection or if a broader response early in infection then leads to selection of particular CD8+ T cells into the long term memory pool (clonal focussing). In two immunocompetent donors and two renal transplant recipients, the early primary HCMV CD8+ peptide-specific T cell pool was composed of multiple T cell receptor (TcR) Vβ family members. This usage rapidly focused predominantly onto T cell clones bearing a single TcR Vβ family. Clones within the dominant TcR Vβ family frequently had public TcR usage (sequence motifs shared between different unrelated donors) whilst subdominant clones and clones which were contracted below the limit of detection often expressed private TcRs. A high TcR avidity for a particular MHC/peptide could be a factor which governs selection of particular T cells into the memory pool. Functional avidities were determined for multiple virus specific T cell clones and it was clear that T cells specific to the same MHC/peptide combination had very high avidities which were very similar regardless of the donor origin. The expression of particular Natural Killer receptors (NKRs) on CD8+ T cells has also been associated with entry into the virus-specific memory pool. Different repertoires of NKR expression were detected on pp65-specific clones generated during primary infection than on clones generated in long-term memory. Overall this work demonstrates that the HCMV specific CD8+ T cell repertoire seen in long-term virus carriers is established early following primary infection by the rapid selection of public TcR clonotypes which display high functional avidity and often have common NKR expression.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available