Defective antigen processing in GILT-free mice

Processing of proteins for major histocompatibility complex (MHC) class II- restricted presentation to CD4-positive T lymphocytes occurs after they are internalized by antigen-presenting cells (APCs). Antigenic proteins freque ntly contain disulfide bonds, and their reduction in the endocytic pathway facilitates processing. In humans, a gamma interferon-inducible lysosomal t hiol reductase (GILT) is constitutively present in late endocytic compartme nts of APCs. Here, we identified the mouse homolog of GILT and generated a GILT knockout mouse. GILT facilitated the processing and presentation to an tigen-specific T cells of protein antigens containing disulfide bonds. The response to hen egg lysozyme, a model antigen with a compact Structure cont aining four disulfide bonds, was examined in detail.