Thermodynamic characterization of dissociation rate variations of human leukocyte antigen and peptide complexes.

Stability of minor histocompatibility antigen-MHC molecule complexes is a major requirement for the successful presentation of the antigen to T cell receptors. In this letter we show thermodynamic features of the complexes made of a peptide antigen and its three variants to explain molecular basis of variable stability of the complexes. Our analysis suggests that enthalpy is a major factor in determining the stability of the complexes. We also found that the dissociation of the peptides from the complexes exhibits enthalpy-entropy compensation. Two structural features of the complexes, noncovalent chemical bondings and flexibility of the peptides in the complexes, are in a good agreement with our thermodynamic analysis. We expect thermodynamic investigation of peptide antigen-MHC protein complexes will provide valuable information on the stability.