Hindering auxiliary anchors are potent modulators of peptide binding and selection by I-A(k) class II molecules

Selection of particular antigen-derived peptides by class II MHC molecules determines the population of complexes represented on the antigen-presenting cell surface and available for T cell receptor engagement. This discriminating selection process results from unique interactions between the spectrum of peptides generated during antigen processing and the MHC molecules. Here, we examined the selection of peptides by the class II MHC, I-A(k). Our results indicate that although peptide primary anchors are key in MHC binding, auxiliary anchors are a powerful regulatory component in the selection of peptides by I-A(k). Study of the segments surrounding the dominant hen egg white lysozome(48-61) epitope demonstrates that auxiliary anchors also are involved in determining the binding register of I-A(k) along an extended peptide. In addition, we found that unique combinations of auxiliary anchors can act in concert to modulate the binding of peptides to I-A(k).