Helper T-cell Epitope Immunodominance Associated with Structurally Stable Segments of Hen Egg Lysozyme and HIV gp120

Abstract

Although many antigen sequences potentially can bind to the MHCII proteins, only a small number of epitopes dominate the immune response. Additional mechanisms of processing, presentation or recognition must restrict the immune response against a large portion of the antigen. A highly significant correlation is found between epitope immunodominance and local structural stability in hen egg lysozyme. Since antigen proteins are likely to retain substantial native-like structure in the processing compartment, protease action may be focused on regions that are most readily accommodated in the protease active sites, and thus, the intervening sequence are preferentially presented. Immunodominance also correlates with sequence conservation as expected from the constraints imposed by structure. These results suggest that the three-dimensional structure of the antigen limits the immune response against some antigen segments. For HIV gp120, a substantial improvement in the accuracy of epitope prediction is obtained by combining rules for MHCII binding with a restriction of the predicted epitopes to well-conserved sequences.