HLA class I transgenic mice: development, utilisation and improvement

Classical major histocompatibility complex (MHC) class I antigens are trimeric molecules found on the surface of nucleated cells in all jawed vertebrates. MHC I are recognised by two families of receptors: clonotypic T cell receptors expressed on the surface of CD8+ cytotoxic T lymphocytes (CTLs), and monomorphic receptors expressed by both natural killer cells and CTLs. The production of MHC I molecules within the cells is a sequential process performed with the help of interacting proteins: proteases, chaperones, transporters and so on. Although largely homologous in their structure, organisation and function, the human and mouse MHC I antigen processing and presentation machineries show fine differences. Transgenesis and ‘knockout’ or ‘knock-in’ technologies permit the addition of relevant human genes or the replacement of mouse genes by their human orthologues in order to produce immunologically humanised mice. Such experimental animals are especially relevant for the comparative evaluation of immunotherapies and for the characterisation of MHC I peptide epitopes. This review presents the similarities and differences between mouse and human MHC I antigen processing machinery, and describes the development and utilisation of improving mouse models of human cytotoxic T cell immunity.