Differential stability of HLA-DR alleles independent of endogenous peptides.

ABSTRACT

Purified HLA DRB1*0101 was shown to be inherently more stable to dissociation than DRB1*0401. The residues responsible for the differential stability were defined by constructing hybrid molecules, which contained a small number of residues from DRB1*0101 substituted into the framework of DRB1*0401. One of the hybrid molecules, containing six substituted amino acids, was as stable as DRB1*0101, but exhibited the binding specificity of DRB1*0401. This result indicated that the differential stability between the alleles arose from structural differences, and was not due solely to varying populations of endogenous peptides.