In a normal animal, Class II MHC proteins bind a large variety of peptides in their peptide-binding grooves. In transgenic animals created in our lab, it has been observed that in the absence of invariant chain, animals can be produced which have only one MHC/peptide combination in the entire animal (L. Ignatowicz, et al in press). However, in animals that differ only by the presence of the invariant chain, a large variety of peptides are presented in the groove of the single Class n MHC protein present. Since it has been postulated that the invariant chain binds yia the same peptide binding groove whereby the Class n MHC protein binds peptide, it was of interest to determine in what manner invariant chain is involved in this interaction. Splenccytes from these animals have been subjected to immunoprecipitation and Western blotting, and it has been determined that invariant chain can bind to properly folded IAb-Ect protein, as recognized by YAe, an antibody which is specific for IAb containing Ea in the peptide binding groove. This lends credence to the hypothesis that the invariant chain binds to Class n MHC protein, even when the peptide binding groove is already occupied by the covalently bound peptide, and this causes it to move to the surface via the endosome, causing the peptide linker to be cleaved, with subsequent replacement by other peptides. It also raises questions about the hypothesis that the invariant chain always binds to Class n MHC in the peptide binding groove.
|Original language||English (US)|
|Publication status||Published - Dec 1 1996|
ASJC Scopus subject areas
- Molecular Biology