A ‘first loop’ linear epitope accessible on native hepatitis B surface antigen that persists in the face of ‘second loop’ immune escape

Abstract

Murine monoclonal antibodies (mAbs) were raised following immunization with native mutant hepatitis B surface antigen (HBsAg) purified from human sera. A set of antibodies binding to a linear epitope carried between residues 121 and 129 of the s region was demonstrated. These antibodies were shown by cross-competition assays to bind to a single epitope whose antigenicity was influenced by the TTP motif lying between residues 125 and 127. This first loop epitope remained accessible on the surface of HBsAg in spite of major second loop mutations abrogating the normal a conformational epitopes. The mAb and its binding region in the first loop are important diagnostically and may represent an importance immunological target, one that is stable in the face of immunologically driven escape.

Ultradeep Sequencing for Detection of Quasispecies Variants in the Major Hydrophilic Region of Hepatitis B Virus in Indonesian Patients

“…The naturally occurring P120T variant has also been detected in some unvaccinated and treated patients (59,60). The variant P127T was reported to reduce the binding of HBsAg to monoclonal antibodies (61). Several variants in the MHR found in this study were the genetic background of HBV genotypes.…”

The genetic backbone modulates the phenotype of hepatitis B surface antigen mutants

“…Consistency of reactivity was seen both within and between genotypes, although within genotype E, reactivity was more variable, resulting in a higher standard deviation for AUC representation. The amino acid consensus sequence of genotype E a determinant carries a distinct motif with a change at sT140S and a non-conservative change at sP127L (Norder et al, 2004), which lies within and potentially alters the P2D3 epitope (Ijaz et al, 2003). A single genotype E sample carrying proline at s127 nevertheless fell close to the genotype mean.…”

“…Three mAbs were used for this. The first, P2D3, recognizes a conserved sequence in the first loop, reacts in Western blotting and binds to a discrete epitope s121-129 (Ijaz et al, 2003). mAbs H3F5 and D2H5 were raised against native HBsAg and reacted equally with all specimens in the Couroucé Paris HBsAg panel (Tedder et al, 1983); they are unreactive in Western blotting but react with conserved 'conformational' epitopes and exhibit limited reactivity in cross-inhibition studies.…”

Variantes de escape del virus de la hepatitis B

“…También se han descrito mutaciones en los residuos 126, 129, 133, 141 y 144 que evitan el reconocimiento del antígeno a pesar de la respuesta humoral en individuos vacunados [32][33][34] .…”