Professor Elizabeth Simpson, FRS
Use of the HY System to Address Basic Questions in Immunology and Immunotherapy
The male-specific minor histocompatibility antigen, HY, encoded by a series of linked genes on the Y chromosome in both mice and humans, is a target for T cell-mediated tissue and organ graft rejection responses but also of graft-versus-host (GVH) and graft-versus-leukaemia (GVL) responses following transplantation of cell populations containing allogeneic haematopoietic stem cells (e.g. bone marrow) from donors matched for major histocompatibility complex (MHC) antigens.
Following our recent discovery that complement components are important for the induction and maintenance of tolerance to skin grafts expressing HY, the mechanisms involved are being investigated. In addition, in collaboration with colleagues, various experimental approaches are being used to identify other factors controlling responsiveness. The longer term aim is to maximise therapeutically useful responses and minimise those that are damaging, such as graft-versus-host disease and rejection of therapeutic grafts.
Current research publications:
Chai JG; James E; Dewchand H; Simpson E; Scott D. (15 May 2004). Transplantation tolerance induced by intranasal administration of HY peptides. Blood. 103:3951-3959. Publisher weblink DOI.
Choi EY, Jung KC, Park HJ, Chung DH, Song JS, Yang SD, Simpson E and Park SH (2005) Thymocyte-thymocyte interaction for efficient positive selection and maturation of CD4 T cells. Immunity 23(4):387-396. Publisher weblink
Ferreira C; Furmanski A; Millrain M; Bartok I; Guillaume P; Lees R; Simpson E; MacDonald HR; et al. (15 Aug 2006). TCR-alpha CDR3 loop audition regulates positive selection. J Immunol. 177:2477-2485. Publisher weblink.
Robertson NJ; Chai JG; Millrain M; Scott D; Hashim F; Manktelow E; Lemonnier F; Simpson E; et al. (15 Mar 2007). Natural regulation of immunity to minor histocompatibility antigens. J Immunol. 178:3558-3565. Publisher weblink.
Furmanski AL; Ferreira C; Bartok I; Dimakou S; Rice J; Stevenson FK; Millrain MM; Simpson E; et al. (15 Jan 2008). Public T cell receptor beta-chains are not advantaged during positive selection. J IMMUNOL. 180:1029-1039. Weblink
Greenlaw RE; Gardner NJ; Farrar CA; Shariff H; Sacks SH; Yagita H; Simpson E; Jurcevic S. (Nov 2008). An antibody combination that targets activated T cells extends graft survival in sensitized recipients. AM J TRANSPLANT. 8:2272-2282. DOI.
Yoon IH; Choi SE; Kim YH; Yang SH; Park JH; Park CS; Kim Y; Kim JS; et al. (27 Nov 2008). Pancreatic Islets Induce CD4(+)CD25(-Foxp3+) T-Cell Regulated Tolerance to HY-Mismatched Skin Grafts. TRANSPLANTATION. 86:1352-1360. DOI.
Baruah P; Dumitriu IE; Malik TH; Cook HT; Dyson J; Scott D; Simpson E; Botto M. (9 Apr 2009). C1q enhances IFN-gamma production by antigen-specific T cells via the CD40 costimulatory pathway on dendritic cells. BLOOD. 113:3485-3493. DOI.
Baruah P, Simpson E, Dumitriu IE, Derbyshire K, Coe D, Addey C, Dyson J, Chai JG, Cook HT, Scott D, Botto M. (8 Mar 2010) Mice lacking C1q or C3 show accelerated rejection of minor H disparate skin grafts and resistance to induction of tolerance. Euro J Immunol, 40(6): 1758 - 1767 DOI
The roles of antigen-specificity, responsiveness to TGFβ and APC subsets in tumour-induced expansion of regulatory T cells. Coe, David; Addey, Caroline; White, Matthew; Simpson, Elizabeth; Dyson, P J; Chai, JG. Immunology, in press 2010
