Mice lacking the MHC class II-associated invariant chain

Area of Science:

• Immunology
• Molecular Biology
• Genetics

Background:

• The invariant chain (li) is closely associated with major histocompatibility complex (MHC) class II molecules.
• Proposed functions of the invariant chain lack definitive experimental proof due to limitations in existing models.

Purpose of the Study:

• To investigate the role of the invariant chain in MHC class II transport and function.
• To generate and analyze mice with a complete deficiency in the invariant chain.

Main Methods:

• Generation of a mouse line with a drastic mutation in the invariant chain (li) gene.
• Analysis of MHC class II molecule transport and surface expression in mutant cells.
• Assessment of antigen presentation capabilities and CD4+ T cell selection in mutant mice.

Main Results:

• Invariant chain-deficient cells exhibit aberrant transport of MHC class II molecules.
• Reduced surface levels and altered conformation of MHC class II complexes were observed in mutant cells.
• Mutant cells demonstrated significantly impaired presentation of protein antigens.
• Mutant mice showed deficiencies in CD4+ T cell production and negative selection.

Conclusions:

• The invariant chain is essential for proper MHC class II trafficking and peptide loading.
• Invariant chain deficiency profoundly impacts antigen presentation and T cell-mediated immunity.
• This study provides definitive evidence for the critical role of the invariant chain in the adaptive immune response.