In the past, our work has focused on determining the genomic structure of the chicken MHC, the sequence polymorphism, peptide motifs and expression levels of MHC molecules, the effect of the dominantly-expressed class I and class II molecules on the immune response, and the development of a conceptual framework to explain the MHC strategy of chickens and other non-mammalian vertebrates in comparison to typical mammals.
Some of this work will continue, but our focus in Cambridge will shift to (1) a detailed understanding of co-evolution between genes of the chicken MHC, (2) the effect of single dominantly-expressed class I and class II molecules on the cells and receptors which recognise them, and (3) the importance of sequence polymorphism, peptide-binding and expression level on disease resistance, vaccine response and other phenomena at an individual and population level.
As a start, we plan (in part with valued collaborators at the Pirbright Institute, the Roslin Institute and the Universities of Cambridge, Copenhagen, Harvard, Munich, Oxford, Queensland, Sheffield, South Denmark and Southampton) to:
- Use molecular biology, biochemistry and cell biology to study the structure and functional relationship of sequence polymorphism in class I genes with the potentially co-evolving TAP, tapasin and B-NK genes, class II B genes with DM genes, and BG genes with their as-yet-unidentified ligands.
- Use molecular biology, biochemistry and cellular immunology to culture dendritic cells, T lymphocytes, NK cells and other important cells, and to study their cell surface molecules, and then determine the relationship between MHC molecules and these cells and receptors.
- Use molecular biology, biochemistry, cellular and whole animal immunology, and epidemiology to study responses to particular pathogens and vaccines, as well as to study the potential importance of the MHC in sexual selection and reproduction.
Most recently, we have been examining how the transmissible tumour that is decimating the Tasmanian devil escapes immune rejection. We have also (with valued collaborators) been extending some of this work to other birds and to certain fish, and to begin to evaluate the contribution of other loci to the immune response of chickens.
- Group Members:
Xaquin Castro Dopico, Andrew Chan, Michael Harrison, Alicia Martin Lopez, El Kahina Meziane, Nicola Potts, Clive Tregaskes & Daniel Wise, Lei Chen
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.