The present invention relates to novel methods of diagnosing, preventing, and treating diseases, disorders, and infections relating to T-cell response. The disclosed methods for predicting MHC class II epitopes that elicit CD4+ T-cell response are N based on the three-dimensional protein structure of an antigen of interest. Given such an antigen, structural properties of the protein taken from experimental and modeling data are used to compute an epitope likelihood score that characterizes the location of epitopes likely to elicit an immune response to CD4+ T-cells. The epitopes are then used to construct biomolecules, including peptides, which may be used to diagnose, prevent, and/or treat a number of diseases, disorders, and infections.
