Human B-cell receptor specific for HIV-1 Envelope glycoprotein (HIV-1 Env-specific BCR)

The human B-cell receptor (BCR) recognizing HIV-1 Envelope (Env) epitopes on the BG505 SOSIP.664 gp140 trimer is a primary target for next-generation HIV-1 vaccine design. BG505 SOSIP.664 is a stabilized, recombinant protein that mimics the native, cleaved trimeric structure of the HIV-1 viral spike, which is the sole target for neutralizing antibodies (Sanders et al., 2013, PLOS Pathogens). By presenting epitopes in a near-native conformation, this target allows for the selective activation of B cells that possess the potential to develop into broadly neutralizing antibodies (bNAbs) (Burton & Hangartner, 2016, Annual Review of Immunology). The interaction between the BCR and the SOSIP trimer triggers B-cell signaling, proliferation, and the process of somatic hypermutation, which is necessary to overcome the virus's extensive glycan shield and genetic diversity (Klasse et al., 2013, Journal of Virology). This target is central to germline-targeting strategies, where specific immunogens are designed to engage rare B-cell precursors that can eventually evolve to neutralize diverse HIV-1 strains (Jardine et al., 2016, Science). Successfully engaging these BCRs is considered a prerequisite for inducing protective immunity against HIV-1 infection. Therapeutic development focuses on using these trimers as immunogens to guide the immune system toward producing high-affinity antibodies against conserved sites of vulnerability on the virus.

Other names

HIV-1 Envelope-specific B-cell receptorBG505 SOSIP-reactive BCRAnti-HIV-1 Env BCRHIV-1 Env-binding B-cell receptor

Antigen-mediated B-cell receptor signaling and clonal expansion leading to affinity maturation of neutralizing antibodies.