RESUMO
This review examines the field of current HLA class II transgenic mouse models and the individual approaches applied in production of these mice. The majority of these mice have been created with the objective of obtaining a disease model with clinical features mimicking human autoimmune disease. The development process of a different type of HLA class II transgenic mice, which are designed to function as a substitute for a normal human immune system in studies of human autoantigens, is described. Several HLA-DR4 transgenic lines with normally expressed HLA-DR4 molecules have been produced. To obtain adequate positive selection of the HLA-DR4-restricted CD4+ T-cell repertoire in these mice it is essential both to introduce a human CD4 transgene, and to delete the murine major histocompatibility complex (MHC) class II molecules. These HLA-DR4 transgenic mice have been used to determine the immunogenic CD4+ T-cell epitopes of several human autoantigenic proteins.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Antígeno HLA-DR4/genética , Camundongos Transgênicos/genética , Camundongos Transgênicos/imunologia , Animais , Autoantígenos/metabolismo , Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , Modelos Animais de Doenças , Antígeno HLA-DR4/metabolismo , Humanos , Camundongos , Modelos BiológicosRESUMO
The interactions of empty recombinant major histocompatibility complex (MHC) class II molecules (DRA1*0101/DRB1*0401) with a known peptide ligand [the HA(307-319) fragment of influenza virus hemagglutinin] were studied by capillary electrophoresis. Using an alkaline buffer system with the addition of non-ionic or zwitterionic detergent and high sensitivity laser-induced fluorescence detection, both slowly and rapidly equilibrating binding could be demonstrated. This was accomplished using a pre-equilibration approach as well as migration shift experiments where receptor molecules were added to the electrophoresis buffer. This system may be useful for the study of both peptide binding to MHC molecules and screening for inhibition or amplification of binding by other ligands as well as for the study of the interactions of T-cell receptors with MHC-peptide complexes.