Our laboratory investigates the relationship of antigen 3D structure to CD4+ T-cell immune responses. Work on HIV envelope glycoprotein gp120 revealed the influence of disulfide bonds on CD4+ T-cell epitope immunodominance and that T-cell-B-cell collaborations can be shaped by epitope-specific peptide priming. Using diverse antigens and various biochemical and biophysical methods, we have demonstrated that protein conformational stability has a major impact on immune responses through its effects on antigen processing. Our recent studies show that optimal conformational stability promotes antibody affinity maturation.