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Professor Jim Kaufman

Professor Jim Kaufman

Professor of Comparative Immunogenetics

Division of Immunology

Project: Structure, function and evolution of the immune response, focusing on the avian MHC

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

Office Phone: +44 (0)1223 766423

Research themes

Genomics:

Division

Immunology:

Research Interests

Kaufman Research

Our lab is interested in the evolution of immunity, focusing on the major histocompatibility complex (MHC) of chickens. In addition to developing scenarios for the evolution of the adaptive immune system, some of our work on genetics and vaccines can underpin the global poultry industry, and we use the simpler MHC-TCR system of chickens to discover phenomena that are more difficult to discern in the more complex systems of mammals.

Among many other discoveries, we have found that the genome organisation of the chicken MHC led to co-evolution of the closely-linked TAP, tapasin and BF2 class I genes, resulting in a single dominantly-expressed class I molecule that can explain the strong genetic associations between the chicken MHC with resistance and susceptibility to economically-important infectious disease. The salient features of the chicken MHC are found in many non-mammalian vertebrates, and we believe that an inversion from this ancestral organisation in the lineage leading to placental mammals led to the textbook picture of the MHC and the way it functions, particularly the relatively weak genetic associations of the human MHC with infectious disease.

More recently, we have found an inverse correlation between cell surface expression and the diversity of peptide binding by class I molecules, both in chickens and humans. In chickens the promiscuous alleles confer more-or-less resistance to many pathogens, while in humans some fastidious alleles confer long-term non-progression from HIV infection to AIDS, the strongest genetic association of the human MHC with infectious disease. Several observations have led to the proposal of class I alleles as generalists versus specialists.

We also examine the class II system, focusing on class II B and DMB genes that are only expressed in particular cell types and searching for unexpected functions. We have set up a high through-put MHC gene typing process, looking at alleles and haplotypes in commercial, fancy, village and wild birds throughout the world. We also examine chicken BG multigene family, which is most closely-related to the butyrophilins and SKINT genes of mammals. We continue our interests in other animals, including sparrows and Tasmanian devils.

Also affiliated with the Department of Veterinary Medicine

  • Group Members:

    Hassnae Afrache, Lei (Joanna) Chen, Felicity (Flic) Coulter, Eve Doran, Samer Halabi, Rebecca (Becky) Martin, Alicia Martin Lopez, Jim Kaufman, Clive Tregaskes & Daniel Wise 

Key Publications

  1. Kaufman, J., Milne, S., Goebel, T. W. F., Walker, B. A., Jacob, J. P., Auffray, C., Zoorob, R. and Beck, S. (1999) The chicken B locus is a minimal essential major histocompatibility complex. Nature 401: 923-925.
  2. Salomonsen, J., Sorenson, M. R., Marston, D. A., Rogers, S. A., Collen, T., van Hateren, A., Smith, A. L, Beal, R. K., Skjødt, K. and Kaufman, J. (2005) From the cover: Two CD1 genes map to the chicken MHC, indicating that CD1 genes are ancient and likely to have been present in the primordial MHC. Proc. Natl. Acad. Sci. USA 102: 8668-8673.
  3. Wallny, H.-J., Avila, D., Hunt, L. G., Powell, T. J., Riegert, P., Salomonsen, J., Skjødt, K., Vainio, O., Vilbois, F., Wiles, M. V., and Kaufman, J. (2006) Peptide motifs of the single dominantly-expressed class I molecule can explain the striking MHC-determined response to Rous sarcoma virus in chickens. Proc. Natl. Acad. Sci. USA 103: 1434-1439.
  4. Koch, M., Camp, S., Collen, T., Avila, D., Salomonsen, J., Wallny, H.-J., van Hateren, A., Hunt, L. G., Jacob, J. P., Johnston, F., Marston, D. A., Shaw, I., Dunbar, P. R., Cerundolo, V. E., Jones, E. Y. and Kaufman, J. (2007) Structures of an MHC class I molecule from B21 chickens illustrate promiscuous peptide binding. Immunity 27: 885-899.
  5. Walker, B. A., Hunt, L. G., Sowa, A. K., Skjødt, K., Goebel, T. W., Lehner, P. J. and Kaufman, J. (2011) The dominantly-expressed class I molecule of the chicken MHC is explained by co-evolution with the polymorphic peptide transporter (TAP) genes. Proc. Natl. Acad. Sci. USA 108: 8396-8401.
  6. Siddle, H. V., Kreiss, A., Tovar, C., Yuen, C. K., Cheng, Y., Belov, K., Swift, K., Pearse, A.-M., Hamede, R., Jones, M. E., Skjødt, K., Woods, G. M. and Kaufman, J. (2013) Reversible epigenetic down-regulation of MHC molecules by Devil Facial Tumour Disease illustrates immune escape by a contagious cancer, Proc. Natl. Acad. Sci. USA 110: 5103-8.
  7. Salomonsen, J., Chattaway, J. A., Chan, A. C. Y., Parker, A., Huguet, S., Marston, D. A. Rogers, S. L., Wu, Z., Smith, A. L., Staines, K.,  Butter, C., Riegert, P., Vainio, O., Nielsen, L., Kaspers, B., Griffin, D. K., Yang, F., Zoorob, R., Guillemot, F., Auffray, C., Beck, S., Skjødt, Kand Kaufman, J. (2014) Sequence of a complete chicken BG haplotype shows dynamic expansion and contraction of two gene lineages with particular expression patterns. PLoS Genetics 10: e1004417.
  8. Chappell, P., Meziane, E. K., Harrison, M., Magiera, Ł., Hermann, C., Mears, L., Wrobel, A. G., Durant, C., Nielsen, L. L., Buus, S., Ternette, N., Mwangi, W., Butter, C., Nair, V., Ahyee, T., Duggleby, R., Madrigal, A., Roversi, P., Lea, S. M. and Kaufman, J. (2015) Expression levels of MHC class I molecules are inversely correlated with promiscuity of peptide binding. eLIFE 4: e05345.
  9. Tregaskes, C. A., Harrison, M., Sowa, A. K., van Hateren, A., Hunt, L. G., Vainio, O. and Kaufman, J. (2016) Surface expression, peptide repertoire and thermostability of chicken class I molecules correlate with peptide transporter specificity. Proc. Natl. Acad. Sci. USA 113: 692-7.
  10. Tovar, C., Pye, R. J., Kreiss, A., Cheng, Y., Brown, G. K., Darby, J., Malley, R. C., Siddle, H. V., Skjødt, K., Kaufman, J., Silva, A., Baz Morelli, A., Papenfuss, A. T., Corcoran, L. M., Murphy, J. M., Pearse, M. J., Belov, K., Lyons, A. B., Woods, G. M. (2017) Regression of devil facial tumour disease following immunotherapy in immunised Tasmanian devils. Sci. Rep. 7: 43827.