Our current understanding of T-cell mediated immunity has been established through the intense study of “conventional” αβ T-cells and the αβ T-cell receptor’s (TCR) remarkable ability to detect pathogen infected cells by recognising foreign peptide antigens presented by major histocompatibility complexes (MHCs). Despite human γδ T-cells being implicated in immunity to infectious diseases, the role of human γδ T-cells and the mechanisms they use to detect infection are largely unclear. γδ T-cells are defined as an innate-like T-cell population, operating outside of peptide/MHC recognition, comprising restricted γδTCR chain usage from birth and rapidly responding to TCR independent stimuli.
In a series of studies, I have developed our understanding of an “unconventional” adaptive immunobiology followed by human γδ T-cells. I have found that the γδ T-cell repertoire can undergo post-natal clonal γδTCR selection in the blood and liver, and can recognise non-peptide antigens in vastly different ways to αβ T-cell receptors. These features contrast markedly with that of an innate-T-cell population, indicating that the γδTCR repertoire may be shaped by microbial exposure to promote immunity.
To explore these facets of the immune system my lab uses cutting-edge immunological techniques, such as spectral flow cytometry, single cell genomics and immune repertoire sequencing, to understand the chain of events that drive the immunobiology of human γδ T-cells and their contribution to maintaining tissue integrity and combating infectious pathogens.
The ultimate aim of my labs work is to establish our ability to design new vaccine strategies to manipulate the γδ T-cell-mediated immune response to promote protection from infectious diseases.
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