B-cell receptor specific for HIV-1 gp120 epitopes (BCR-gp120)

The B-cell receptor specific for HIV-1 gp120 epitopes is a membrane-bound immunoglobulin expressed on the surface of B lymphocytes that recognizes the gp120 subunit of the HIV-1 envelope glycoprotein (Env) (Jardine et al., 2013, Science). These receptors are the primary targets for germline-targeting vaccine strategies, which aim to activate specific B-cell precursors capable of evolving into broadly neutralizing antibodies (bNAbs) (Leggat et al., 2022, Science). Upon binding to gp120 epitopes, such as the CD4 binding site (CD4bs), the BCR initiates intracellular signaling pathways that lead to B-cell proliferation and entry into germinal centers for affinity maturation (Dosenovic et al., 2015, Cell). This target is central to addressing the challenge of HIV-1's extreme sequence diversity and glycan shielding, which typically prevent the induction of effective neutralizing responses (Haynes et al., 2019, Nature Biotechnology). Engineered immunogens like eOD-GT8 60mer are designed to bind with high affinity to these specific BCRs to overcome the low frequency of naturally occurring bNAb precursors in the human repertoire (Cohen, 2022, Science).

Other names

HIV-1 envelope-specific B-cell receptorgp120-reactive B-cell receptorVRC01-class B-cell receptor precursorAnti-gp120 BCR

Germline targeting and activation of specific B-cell lineages to induce somatic hypermutation and affinity maturation toward broadly neutralizing antibody phenotypes.