Class II antigens of the major histocompatibility complex (MHC) are essential in the immune response because they bind processed polypeptides for presentation to T lymphocytes. The interactions of cass II MHC molecules on the antigen-presenting cell with a responding T lymphocyte are complex because they involve molecular contacts with an antigen peptide, an antigen-specific T-cell receptor, and the CD4 molecule expressed on the T lymphocytes. In this context, the majority of peptides bound by MHC class II molecules during antigen loading are not derived from ingested and processed foreign proteins but instead are primarily derived from a finite number of self-proteins. During progression outward through the exocytic pathway in the process of antigen presentation, class II-invariant chain complexes play a critical role. Experimental autoimmune uveoretinitis (EAU) in rodents is a T-cell-mediated autoimmune response, particularly against the photoreceptors of the neural retinal cells, and can serve as a model for human uveitis. The roles of MHC and non-MHC genes have been strongly associated with EAU in rats and mice. To further study the MHC class II participation in the mouse model, we decided to generate deficient mice for the invariant chain gene (li). This glycoprotein combines with MHC class II heterodimers from the beginning of their synthesis in the endoplasmic reticulum, travels through the Golgi apparatus, and ends up in endosomal compartments where it is either proteotypically cleaved or degraded. The absence of li has been shown to affect the transport of class II molecules, resulting in a poor antigen presentation.
