BG18-class germline B cell receptor (BG18-class gBCR)

The BG18-class germline B cell receptor (gBCR) is the unmutated precursor to the BG18 lineage of broadly neutralizing antibodies (bNAbs), which target the N332-dependent V3-glycan supersite on the HIV-1 envelope (Env) protein. These receptors are typically characterized by the usage of specific heavy chain genes, such as VH3-30 or VH3-33, and possess structural features like long heavy-chain complementarity-determining region 3 (HCDR3) loops necessary for penetrating the viral glycan shield. In modern HIV vaccine development, these gBCRs serve as the primary therapeutic targets for germline-targeting immunogens. These engineered vaccines are designed to bind specifically to the gBCR to initiate the activation and maturation of B cells that can eventually produce potent bNAbs. By guiding the immune system through a defined evolutionary pathway of somatic hypermutation, researchers aim to overcome the high mutational diversity of HIV-1. This target is central to structure-based vaccine design strategies seeking to elicit protective immunity in uninfected individuals. (Sok et al., 2016, Science; Steichen et al., 2019, Science; MacCamy et al., 2022, Cell Reports).

Other names

BG18-precursor B cell receptorVH3-33/VH3-30 germline B cell receptorN332-dependent V3-glycan-targeting germline B cell receptorV3-glycan supersite-directed germline BCR

Binding of engineered immunogens to the germline B cell receptor triggers B cell activation, clonal expansion, and affinity maturation toward broadly neutralizing antibody phenotypes.