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Professor John Trowsdale

Professor John Trowsdale

Professor of Immunology

Project: Interactions between polymorphic modulators of immunity

Department of Pathology
University of Cambridge
Tennis Court Road
Cambridge
CB2 1QP

CIMR
Addenbrookes Site
Hills Road
Cambridge
CB2 2XY

Office Phone: +44 (0)1223 330248

Research themes

Immunology:

Research Interests

The human major histocompatibility complex (MHC) encodes the most polymorphic proteins in the human genome and is associated with more diseases than any other region. Unravelling this complex of human loci, from sequence to function, will help to understand autoimmune diseases such as diabetes, multiple sclerosis and arthritis. The class I and class II molecules encoded by the MHC play a pivotal role in alerting the rest of the immune system to disease by interacting with receptors on T cells. A major part of our work concerns these molecules. Other genes embedded in the MHC provide additional clues to mechanisms of immune recognition and we are studying the functions of some of them, including including BTN and a molecule related to tapasin (collaboration with Louise Boyle).

Trowsdale Research
Receptors in the Leukocyte Receptor Complex and some proposed ligands

Further information on the state of health of a cell is provided by interaction of MHC class I molecules with other receptors, on natural killer (NK) cells. Like some MHC genes, the NK receptors are part of extensive gene families. They are involved in activating, or inhibiting NK cells and some T cells. We are studying the organisation of the NK-receptor gene families, their polymorphism and association with disease, particularly in relation to interaction of the receptors with different MHC class I molecules.

Research associates:
Chiwen Chang
Martin Jahnke
Des Jones
Andreas Neerincx

Graduate students:
Shirin Ashraf
Kattria van der Ploeg
Valeria Radjabova

Key Publications

  1. Rhodes DA, Chen HC, Price AJ, Keeble AH, Davey MS, James LC, Eberl M, Trowsdale JActivation of Human γδ T Cells by Cytosolic Interactions of BTN3A1 with Soluble Phosphoantigens and the Cytoskeletal Adaptor Periplakin. J Immunol. 2015. 194:2390-8.
  2. Tapasin-related protein TAPBPR is an additional component of the MHC class I presentation pathway. Boyle LH, Hermann C, Boname JM, Porter KM, Patel PA, Burr ML, Duncan LM, Harbour ME, Rhodes DA, Skjødt K, Lehner PJ, Trowsdale J. Proc Natl Acad Sci U S A. 2013 Feb 26;110(9):3465-70.
  3. Major histocompatibility complex genomics and human disease.
    Trowsdale J, Knight JC. Annu Rev Genomics Hum Genet. 2013;14:301-23.
  4. Butyrophilin Btn2a2 inhibits TCR activation and phosphatidylinositol 3-kinase/Akt pathway signaling and induces Foxp3 expression in T lymphocytes. Ammann JU, Cooke A, Trowsdale J. J Immunol. 2013 May 15;190(10):5030-6.
  5. Copy number variation leads to considerable diversity for B but not A haplotypes of the human KIR genes encoding NK cell receptors. Jiang W, Johnson C, Jayaraman J, Simecek N, Noble J, Moffatt MF, Cookson WO, Trowsdale J, Traherne JA.
    Genome Res. 2012 Oct;22(10):1845-54.
  6. Influence of KIR gene copy number on natural killer cell education. Béziat V, Traherne JA, Liu LL, Jayaraman J, Enqvist M, Larsson S, Trowsdale J, Malmberg KJ.
    Blood. 2013 Jun 6;121(23):4703-7.