| Citation | Colin Watts has been at the forefront of the drive to understand how exogenous antigens are captured by antigen-presenting cells, and then processed and presented on MHC molecules. He was the first to demonstrate that antigen bound to B lymphocyte surface immunoglobulin is endocytosed via clathrin coated pits and delivered to specialised compartments of the endosome/lysosome system. He showed that antigen proteolysis and in turn peptide capture by MHC molecules, can be modulated by the specificity of the B cell's surface immunoglobulin. He has made major contributions to our understanding of the loading and display of peptide/class II MHC complexes, showing that processed antigen is captured by newly synthesised class II MHC molecules and, with A Lanzavecchia, that this binding is essentially irreversible ensuring that antigen presentation, by dendritic cells, can occur long after antigen capture. More recently, he discovered the novel cysteine proteinase AEP as the enzyme performing the initiating and rate-limiting step in processing and presentation of the tetanus toxin antigen. This provided the first evidence that a specific enzyme is required for processing antigen in the class II MHC pathway. Contrary to expectation, this work has demonstrated that a single proteolytic cleavage site can be crucial for efficient presentation of many T-cell epitopes in an antigen which has triggered interest in the possibility that inhibition of AEP or other processing proteases may
block presentation of allergens and autoantigens. Finally, his roup were the first to demonstrate that antigen pinocytosed by dentritic cells could be shuttled into the cytosol leading to `cross-presentation' on class I MHC molecules. |