Mice lacking H2-M complexes in the context of different MHC haplotypes

Major histocompatibility complex (MHC) class II molecules bind peptides derived from extracellular pathogens and present them to CD4 + T lymphocytes. MHC class II glycoprotein assembly initiates in the endoplasmatic reticulum (ER) by the association of class II a b dimers with a third polypeptide termed the invariant chain (li). li blocks most peptides from binding to class II molecules in the ER and directs their egress from the ER and targeting to endocytic compartments. In their acidic enviroment, li is exchanged for antigenic peptides by DM molecule in human or H2-M in mouse. Class II-peptide complexes are then transported to the cell surface. H2b haplotype mice carrying a null allele in H2-M are defective in class II peptide loading, antigen presentation, and CD4 + T cell selection. Recent evidence suggest that highly polymorphic class II alleles differ with regard to their dependence on H2-M. However, these observations have been made using in vitro and transfection assays influenced by numerous parameters. The aim of this project is to create H2-M mutant mouse strains carrying different MHC haplotypes. The structure and function of class II molecules produced by H2-M mutant mice carrying the H-2k and H-2d alleles, as well as their antigen presentation capabilities and T cell responses will be characterized.