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Department of Pathology

 
Project: Interactions between polymorphic modulators of immunity

Research

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.

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 Associate:
Mumtaz Naiyer

Postdocs:
James Traherne

Research Assistant:
Vitalina Kirgizova

Publications

Key publications: 
  1. Inhibitory killer cell immunoglobulin-like receptors strengthen CD8+ T cell-mediated control of HIV-1, HCV, and HTLV-1.
    Boelen L, Debebe B, Silveira M, Salam A, Makinde J, Roberts CH, Wang ECY, Frater J, Gilmour J, Twigger K, Ladell K, Miners KL, Jayaraman J, Traherne JA, Price DA, Qi Y, Martin MP, Macallan DC, Thio CL, Astemborski J, Kirk G, Donfield SM, Buchbinder S, Khakoo SI, Goedert JJ, Trowsdale J, Carrington M, Kollnberger S, Asquith B. Sci Immunol. 2018 Nov 9;3(29).

  2. High-Resolution Genetic and Phenotypic Analysis of KIR2DL1 Alleles and Their Association with Pre-Eclampsia.
    Huhn O, Chazara O, Ivarsson MA, Retière C, Venkatesan TC, Norman PJ, Hilton HG, Jayaraman J, Traherne JA, Trowsdale J, Ito M, Kling C, Parham P, Ghadially H, Moffett A, Sharkey AM, Colucci F. J Immunol. 2018 Nov 1;201(9):2593-2601.

  3. Regulation of Human γδ T Cells by BTN3A1 Protein Stability and ATP-Binding Cassette Transporters.
    Rhodes DA, Chen HC, Williamson JC, Hill A, Yuan J, Smith S, Rhodes H, Trowsdale J, Lehner PJ, Herrmann T, Eberl M. Front Immunol. 2018 Apr 4;9:662.

  4. Modulation of Human Leukocyte Antigen-C by Human Cytomegalovirus Stimulates KIR2DS1 Recognition by Natural Killer Cells.
    van der Ploeg K, Chang C, Ivarsson MA, Moffett A, Wills MR, Trowsdale J.
    Front Immunol. 2017 Mar 29;8:298. 

  5. Control of immune ligands by members of a cytomegalovirus gene expansion suppresses natural killer cell activation.
    Fielding CA, Weekes MP, Nobre LV, Ruckova E, Wilkie GS, Paulo JA, Chang C, Suárez NM, Davies JA, Antrobus R, Stanton RJ, Aicheler RJ, Nichols H, Vojtesek B, Trowsdale J, Davison AJ, Gygi SP, Tomasec P, Lehner PJ, Wilkinson GW.
    Elife. 2017 Feb 10;6. pii: e22206.

  6. Defining KIR and HLA Class I Genotypes at Highest Resolution via High-Throughput Sequencing.
    Norman PJ, Hollenbach JA, Nemat-Gorgani N, Marin WM, Norberg SJ, Ashouri E, Jayaraman J, Wroblewski EE, Trowsdale J, Rajalingam R, Oksenberg JR, Chiaroni J, Guethlein LA, Traherne JA, Ronaghi M, Parham P.
    Am J Hum Genet. 2016 Aug 4;99(2):375-91.

Division of Immunology
Emeritus Professor
Professor John  Trowsdale

Contact Details

Department of Pathology
University of Cambridge
Tennis Court Road
Cambridge
CB2 1QP
+44 (0)1223 330248
Not available for consultancy

Affiliations

Departments and institutes: 
Person keywords: 
Immunology
Histocompatibility
MHC
Natural killer cell receptors
Immune system