Martin Davey
Technical Summary
Our current understanding of T-cell mediated immunity has been established through the intense study of 鈥渃onventional鈥 伪尾 T-cells and the 伪尾 T-cell receptor鈥檚 (TCR) remarkable ability to detect pathogen infected cells by recognising foreign peptide antigens presented by major histocompatibility complexes (MHCs). Despite human 纬未 T-cells being implicated in immunity to infectious diseases, the role of human 纬未 T-cells and the mechanisms they use to detect infection are largely unclear. 纬未 T-cells are defined as an innate-like T-cell population, operating outside of peptide/MHC recognition, comprising restricted 纬未TCR chain usage from birth and rapidly responding to TCR independent stimuli.
In a series of studies, I have developed our understanding of an 鈥渦nconventional鈥 adaptive immunobiology followed by human 纬未 T-cells. I have found that the 纬未 T-cell repertoire can undergo post-natal clonal 纬未TCR selection in the blood and liver, and can recognise non-peptide antigens in vastly different ways to 伪尾 T-cell receptors. These features contrast markedly with that of an innate-T-cell population, indicating that the 纬未TCR 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 纬未 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 纬未 T-cell-mediated immune response to promote protection from infectious diseases.
Selected publications:
1. McMurray JL, von Borstel A, Taher TE., Syrimi E, Taylor GS., Sharif M, Rossjohn J, Remmerswaal, EBM, Bemelman FJ, Vieira Braga FA, Chen X, Teichmann SA, Mohammed F, Berry AA, Lyke KE, Williamson KC, Stubbington MJT, Davey MS*, Willcox CR* & Willcox BE*. Transcriptional profiling of human V未1 T cells reveals a pathogen-driven adaptive differentiation program. 2022. .
2. von Borstel A, Chevour P, Arsovski D, Krol JMM, Howson LJ, Berry AA, Day Cl, Ogongo P, Ernst, JD, Nomicos EYH, Boddey JA, Giles EM, Rossjohn J, Traore B, Lyke KE, Williamson KC, Crompton PD & Davey MS. Repeated Plasmodium falciparum infection in humans drives the clonal expansion of an adaptive 纬未 T cell repertoire. 2021. .
3. Rice MT, von Borstel A, Chevour P, Awad W, Howson LJ, Littler DR, Gherardin NA, Le Nours, J, Giles EM, Berry R, Godfrey DI, Davey MS*, Rossjohn J* & Gully BS*. Recognition of the antigen-presenting molecule MR1 by a V未3+ 纬未 T cell receptor. 2021. .
4. Davey MS, Willcox CR, Baker AT, Hunter S, Willcox BE. Recasting human V未1+ T cells in an adaptive role. 2018. .
5. Davey MS, Willcox CR, Hunter S, Kasatskaya SA, Remmerswaal EBM, Salim M, et al. The human V未2(+) T-cell compartment comprises distinct innate-like V纬9(+) and adaptive V纬9(-) subsets. 2018. .
6. Hunter S*, Willcox CR*, Davey MS*, Kasatskaya SA, Jeffery HC, Chudakov DM, Oo YH and Willcox BE. Human liver infiltrating 纬未 T cells are composed of clonally expanded circulating and tissue-resident populations. 2018. .
7. Davey MS, Willcox CR, Joyce SP, Ladell K, Kasatskaya SA, McLaren JE, et al. Clonal selection in the human V未1 T cell repertoire indicates 纬未 TCR-dependent adaptive immune surveillance. 2017. .
