VH1-2*02 VRC01-class germline B cell receptor (VH1-2*02 VRC01-class BCR)

The VH1-2*02 VRC01-class germline B cell receptor (BCR) is the unmutated precursor of a potent class of broadly neutralizing antibodies (bnAbs) that target the CD4 binding site (CD4bs) of the HIV-1 envelope glycoprotein (Env) (Zhou et al., 2010, Science). These receptors are defined by their use of the VH1-2*02 heavy chain gene segment, which provides the structural basis for mimicking the CD4 receptor's interaction with HIV-1 (Jardine et al., 2013, Science). In modern vaccine design, these BCRs are considered the primary target for "germline-targeting" immunogens, such as the eOD-GT8 60mer nanoparticle, which are engineered to bind these rare naive B cells with high affinity (Schief et al., 2023, Science). The biological role of these receptors is to initiate the immune response that, through a series of guided vaccinations, can lead to the production of mature VRC01-class bnAbs capable of neutralizing a wide range of HIV-1 variants (Bonsignori et al., 2016, Immunity). Because these naive B cells are present at very low frequencies in the human repertoire, they represent a significant challenge for traditional vaccine approaches, necessitating the use of highly specific molecular probes and immunogens (Leggat et al., 2022, Nature Immunology). Successful engagement of these receptors is considered a critical first step in a multi-stage vaccination process designed to elicit VRC01-class bnAbs.

Other names

VRC01-class germline precursorsVH1-2*02 naive B cell receptorsCD4bs-directed germline BCRsVRC01-class unmutated common ancestors

Germline targeting to initiate the development of broadly neutralizing antibodies by binding and activating specific naive B cell precursors.