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.

The contribution of HLA class I antigens in immune status following two doses of rubella vaccination

“…The humoral antibody responses are predominantly directed against rubella virus E1 and E2 glycoproteins [9,10]. Additionally, rubella E1 protein has been demonstrated to be the most important rubella virus antigen to which the majority of the human population develops a lymphocyte proliferative response [11].…”

Change in epitope sites of Mumps orthorubulavirus resources of the National Culture Collection for Pathogens in Korea

“…Other studies have also reported that the mutations in T cell epitope and glycosylation sites could eliminate the neutralizing capacity in a different type of virus [23][24] to suggest a potential effect on the ability of antibodies induced by the MUV vaccine strain to neutralize wild-type viral strains.…”

Diversity of the BoLA-DRB3 Gene in Cattle Breeds From Tropical and Subtropical Regions of South America

“…This conservation extends to the breeds studied here, and is particularly evident in aminoacids at positions 70, 71, and 74 of pocket 4, which occupies a central position within the peptide binding groove. These aminoacids have been implicated as playing a signi cant role in human immune responsiveness (58), but also correlated with vaccine responses and infectious disease susceptibility or tolerance in bovines (55,(59)(60)(61). In this sense, it could be hypothesized that eventhough bovine breeding programs make use of extensive crossing, there may be a functional constraint in the PBR to BoLA-DRB3 aminoacid variability.…”