Research
I am interested in dynamic processes in normal and abnormal immunity, antigen presentation by MHC molecules, and genotype/phenotype interactions in complex disorders, as exemplified by MHC associations with autoimmunity. MHC molecules are highly polymorphic and present diverse self and foreign peptides for recognition by T-cell antigen receptors during development, homeostasis, and activation. We have developed novel ways of tracking the post-translational fate of specific MHC alleles in normal antigen-presenting cells, using heavy water labelling and peptide mass spectrometry. We are now testing the hypothesis that MHC alleles associated with certain autoimmune diseases confer altered turnover, and that this matters for autoimmune pathogenesis. Our techniques are broadly applicable to studies of protein and cell dynamics, with many uses in autoimmune disease research, e.g. measuring fibrogenesis in systemic sclerosis or T-cell turnover in Sjogren's syndrome.
Publications
De Riva A, Deery MJ, McDonald S, Lund T, Busch R (2010) Measurement of protein synthesis using heavy water labeling and peptide mass spectrometry: Discrimination between major histocompatibility complex allotypes Anal Biochem 403(1-2): 1-12
Burster T, Macmillan H, Hou T, Schilling J, Truong P, Boehm BO, Zou F, Lau K, Strohman M, Schaffert S, Busch R, Mellins ED, 2010. Masking of a cathepsin G cleavage site in vivo contributes to the proteolytic resistance of MHC class II molecules. Immunology, 130:436–446.
Busch R *, Neese RA*, Awada M, Hayes GM, Hellerstein MK (2007) Measurement of cell proliferation by heavy water labeling Nat Protoc 2:3045-3057. (* Joint first authors)
Busch R, Rinderknecht CH, Roh S, Lee AW, Harding JJ, Burster T, Hornell TM, Mellins ED (2005) Achieving stability through editing and chaperoning: Regulation of MHC class II peptide binding and expression Immunol Rev 207:242-260
