Point Mutation of a Rubella Virus E1 Protein T-Cell Epitope by Substitution of Single Amino Acid Reversed the Restrictive HLA-DR Polymorphism: A Possible Mechanism Maintaining HLA Polymorphism

Abstract

The influence of single amino acid substitutions within a rubella E1 protein T-cell epitope, E1(273–284) on T-cell recognition was studied. Substitutions of an uncharged amino acid A for an E or for a T and substitution of a T for S were found to not significantly reduce the T-cell responses. However, substitution of a charged residue such as E for hydrophobic residues (I, V, or W); D for Q; or a relatively larger size amino acid for polar residues completely abolished the cytotoxicities mediated by E1(273–284)-specific T-cell clone. A set of single amino acid-substituted peptide analogs of E1(273–284) not eliciting cytotoxicity of the T-cell clone was used to test the influence of point mutation of the epitope on HLA DR restrictions. A panel of B-cell lines with different DR4 subtypes was used as targets in cytotoxicity assays to determine the restrictive HLA molecules. Results showed that modification of the T-cell epitope by point mutation could reverse the HLA DR restriction from one allele to other alleles. A model based on these results has been proposed to explain the mechanism balancing major histocompatibility complex (MHC) polymorphism in outbred populations.