WIMM PI
Curriculum Vitae
Personal Data
Name
Nationality
Email
Alain Robert Michael Townsend
UK
twosned@gmail.com
Current post
Source of Funding
Current address
Postal Address
Professor of Molecular Immunology Oxford
Oxford University
Nuffield Department of Medicine, Oxford University
Room 368 Weatherall Institute, John Radcliffe Hospital,
Headington, Oxford, OX3 9DS
Professional Qualifications
MBBS 1977, MRCP 1979, Ph.D 1984
Clinical Activity
Retrained in acute general medicine 1994-1998,
Consultant Physician 1998-2004.
Educational qualifications
PhD Immunology, London University, 1984
MRCP Medicine, London University, 1979
MBBS, St Mary’s Hospital, London University, 1977
Previous posts held
Ad Hominem Professor of Immunology at Oxford
University, (1992 - Present )
New Blood Lecturer at Oxford University, (1986 -1992)
Clinical Lecturer Oxford (1983 - 1986)
MRC Training Fellow (1980 -1983)
Junior Medical Posts (1977 - 1980)
Career Summary
1979-1997
During this period my main interest lay in understanding the function of the Major
Histocompatibility Complex, particularly with respect to infectious disease and autoimmunity.
I worked initially with Influenza Virus infections in inbred strains of mice and in a series of
papers showed that the viral proteins and by implication all cellular proteins are degraded in
the cytosol, and the derived peptides exposed on the cell surface bound to class I molecules
of the MHC (1984-1986). The same year Bjorkman published the molecular structure of HLA
A2 which revealed the peptide-binding site lying between the two N-terminal domains. I had
earlier shown that the movement of the viral peptide fragments out of the cytosol was
independent of a defined leader sequence. From 1986-1997 with various collaborators I
identified mutant cell lines that lacked the peptide transport function, and showed that
transport depended on a heterodimeric "ABC "transporter also encoded in the MHC, and
further demonstrated that the peptide plays a structural role in the class I molecule by
stabilising the association with beta-2 microglobulin.
1996-2004
In 1994 I began to retrain in clinical medicine, and expanded my interest in class I molecules
to include HFE and its role in iron metabolism. My group has defined a new function for HFE
in the inhibition of release of iron from monocytic cells, and shown that the H63D mutation
that is associated with iron overload in man abolishes this function. We are now looking for
cellular proteins that interact with HFE. We have also worked extensively on rare forms of
iron overload associated with mutations in the iron exporter Ferroportin (FPN) and defined
two classes of mutations associated with two phenotypes. The simplest are mutations which
prevent the inhibition of Ferroportin by Hepcidin thus resulting in iron overload, the others
inactivate FPN to varying degrees. In the latter cases we are trying to understand why
patients bearing an inactivating mutation should become iron loaded.
2004-2012
In 2004 I suffered an illness that kept me off work for several months. I decided then to
return to the laboratory full time. During this period I have continued our interest in Hfe, and
with the recent influenza pandemic I have been considering practical applications of my
earlier work to the issue of whether heterotypic immunity (between pandemic strains) can be
induced in man with live attenuated strains of influenza. This would be of value to mitigate
the first wave of pandemic infection prior to the production of subunit vaccine. We have
developed our own design of pseudotyped influenza virus that relies on mutations in the
haemagglutinin signal sequence that are permissive for infection but prevent replication of
the virus. The advantage of this approach is that all of the viral proteins are expressed in
their appropriate context in the lung, and thus can induce a full set of local innate and
adaptive T and B cell responses. Preliminary results show that our non-replicating viruses
are capable of inducing heterotypic immunity and preventing illness caused by the most
virulent form of influenza in a murine infection model. As part of a broader interest in human
immunity to influenza we are optimising the isolation of human monoclonal antibodies that
neutralise the virus with a view to investigating their potential as therapeutic agents in severe
influenza infections.
Key Publications
Antigen Presentation (* selected for Pillars of Immunology collection by J. Immunol).
Townsend, A.R. & Skehel, J.J. 1982, "Influenza A specific cytotoxic T-cell clones that do not
recognize viral glycoproteins", Nature, vol. 300, no. 5893, pp. 655-657.
Townsend, A.R. & Skehel, J.J. 1984, "The influenza A virus nucleoprotein gene controls the
induction of both subtype specific and cross-reactive cytotoxic T cells", The Journal of
experimental medicine, vol. 160, no. 2, pp. 552-563.
Townsend, A.R., McMichael, A.J., Carter, N.P., Huddleston, J.A. & Brownlee, G.G. 1984,
"Cytotoxic T cell recognition of the influenza nucleoprotein and hemagglutinin expressed
in transfected mouse L cells", Cell, vol. 39, no. 1, pp. 13-25.
Townsend, A.R., Gotch, F.M. & Davey, J. 1985, "Cytotoxic T cells recognize fragments of
the influenza nucleoprotein", Cell, vol. 42, no. 2, pp. 457-467.
Townsend, A.R., Bastin, J., Gould, K. & Brownlee, G.G. 1986, "Cytotoxic T lymphocytes
recognize influenza haemagglutinin that lacks a signal sequence", Nature, vol. 324, no.
6097, pp. 575-577.
*Townsend, A.R., Rothbard, J., Gotch, F.M., Bahadur, G., Wraith, D. & McMichael, A.J.
1986, "The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes
can be defined with short synthetic peptides", Cell, vol. 44, no. 6, pp. 959-968.
Townsend, A., Bastin, J., Gould, K., Brownlee, G., Andrew, M., Coupar, B., Boyle, D., Chan,
S. & Smith, G. 1988, "Defective presentation to class I-restricted cytotoxic T lymphocytes
in vaccinia-infected cells is overcome by enhanced degradation of antigen", The Journal
of experimental medicine, vol. 168, no. 4, pp. 1211-1224.
*Townsend, A., Ohlen, C., Bastin, J., Ljunggren, H.G., Foster, L. & Karre, K. 1989,
"Association of class I major histocompatibility heavy and light chains induced by viral
peptides", Nature, vol. 340, no. 6233, pp. 443-448.
Townsend, A. & Bodmer, H. 1989, "Antigen recognition by class I-restricted T lymphocytes",
Annual Review of Immunology, vol. 7, pp. 601-624.
Gould, K., Cossins, J., Bastin, J., Brownlee, G.G. & Townsend, A. 1989, "A 15 amino acid
fragment of influenza nucleoprotein synthesized in the cytoplasm is presented to class Irestricted cytotoxic T lymphocytes", The Journal of experimental medicine, vol. 170, no. 3,
pp. 1051-1056.
Townsend, A., Elliott, T., Cerundolo, V., Foster, L., Barber, B. & Tse, A. 1990, "Assembly of
MHC class I molecules analyzed in vitro", Cell, vol. 62, no. 2, pp. 285-295.
Cerundolo, V., Alexander, J., Anderson, K., Lamb, C., Cresswell, P., McMichael, A., Gotch,
F. & Townsend, A. 1990, "Presentation of viral antigen controlled by a gene in the major
histocompatibility complex", Nature, vol. 345, no. 6274, pp. 449-452.
*Trowsdale, J., Hanson, I., Mockridge, I., Beck, S., Townsend, A. & Kelly, A. 1990,
"Sequences encoded in the class II region of the MHC related to the 'ABC' superfamily of
transporters", Nature, vol. 348, no. 6303, pp. 741-744.
Powis, S.J., Townsend, A.R., Deverson, E.V., Bastin, J., Butcher, G.W. & Howard, J.C.
1991, "Restoration of antigen presentation to the mutant cell line RMA-S by an MHClinked transporter", Nature, vol. 354, no. 6354, pp. 528-531.
Elvin, J., Cerundolo, V., Elliott, T. & Townsend, A. 1991, "A quantitative assay of peptidedependent class I assembly", European journal of immunology, vol. 21, no. 9, pp. 20252031.
Kleijmeer, M.J., Kelly, A., Geuze, H.J., Slot, J.W., Townsend, A. & Trowsdale, J. 1992,
"Location of MHC-encoded transporters in the endoplasmic reticulum and cis-Golgi",
Nature, vol. 357, no. 6376, pp. 342-344.
Kelly, A., Powis, S.H., Kerr, L.A., Mockridge, I., Elliott, T., Bastin, J., Uchanska-Ziegler, B.,
Ziegler, A., Trowsdale, J. & Townsend, A. 1992, "Assembly and function of the two ABC
transporter proteins encoded in the human major histocompatibility complex", Nature, vol.
355, no. 6361, pp. 641-644.
Cerundolo, V., Kelly, A., Elliott, T., Trowsdale, J. & Townsend, A. 1995, "Genes encoded in
the major histocompatibility complex affecting the generation of peptides for TAP
transport", European journal of immunology, vol. 25, no. 2, pp. 554-562.
Elliott, T., Willis, A., Cerundolo, V. & Townsend, A. 1995, "Processing of major
histocompatibility class I-restricted antigens in the endoplasmic reticulum", The Journal of
experimental medicine, vol. 181, no. 4, pp. 1481-1491.
Cerundolo, V., Benham, A., Braud, V., Mukherjee, S., Gould, K., Macino, B., Neefjes, J. &
Townsend, A. 1997, "The proteasome-specific inhibitor lactacystin blocks presentation of
cytotoxic T lymphocyte epitopes in human and murine cells", European journal of
immunology, vol. 27, no. 1, pp. 336-341.
Springer, S., Doring, K., Skipper, J.C., Townsend, A.R. & Cerundolo, V. 1998, "Fast
association rates suggest a conformational change in the MHC class I molecule H-2Db
upon peptide binding", Biochemistry, vol. 37, no. 9, pp. 3001-3012.
Iron Metabolism
Drakesmith, H., Sweetland, E., Schimanski, L., Edwards, J., Cowley, D., Ashraf, M., Bastin,
J. & Townsend, A.R. 2002, "The hemochromatosis protein HFE inhibits iron export from
macrophages", Proceedings of the National Academy of Sciences of the United States of
America, vol. 99, no. 24, pp. 15602-15607.
Drakesmith, H., Schimanski, L.M., Ormerod, E., Merryweather-Clarke, A.T., Viprakasit, V.,
Edwards, J.P., Sweetland, E., Bastin, J.M., Cowley, D., Chinthammitr, Y., Robson, K.J. &
Townsend, A.R. 2005, "Resistance to hepcidin is conferred by hemochromatosisassociated mutations of ferroportin", Blood, vol. 106, no. 3, pp. 1092-1097.
Schimanski, L.M., Drakesmith, H., Merryweather-Clarke, A.T., Viprakasit, V., Edwards, J.P.,
Sweetland, E., Bastin, J.M., Cowley, D., Chinthammitr, Y., Robson, K.J. & Townsend,
A.R. 2005, "In vitro functional analysis of human ferroportin (FPN) and hemochromatosisassociated FPN mutations", Blood, vol. 105, no. 10, pp. 4096-4102.
Schimanski, L.M., Drakesmith, H., Talbott, C., Horne, K., James, J.R., Davis, S.J.,
Sweetland, E., Bastin, J., Cowley, D. & Townsend, A.R. 2008, "Ferroportin: lack of
evidence for multimers", Blood cells, molecules & diseases, vol. 40, no. 3, pp. 360-369.
Schimanski, L.M., Drakesmith, H., Sweetland, E., Bastin, J., Rezgui, D., Edelmann, M.,
Kessler, B., Merryweather-Clarke, A.T., Robson, K.J. & Townsend, A.R. 2009, "In vitro
binding of HFE to the cation-independent mannose-6 phosphate receptor", Blood cells,
molecules & diseases, vol. 43, no. 2, pp. 180-193.
Markers of Esteem
Cheadle Medal in Medicine St Mary’s Hospital 1977
Cancer Research Institute Award and Medal 1989
Louis Jeantet Prize 1992
Fellowship of the Royal Society 1992
Gairdner Foundation Award 2000