B cell receptors and T cell receptors recognizing influenza hemagglutinin epitopes (BCR/TCR-HA)

B cell receptors (BCRs) and T cell receptors (TCRs) that recognize hemagglutinin (HA) epitopes are the fundamental components of the adaptive immune system targeted by influenza vaccines (Krammer, 2019 [1]). Hemagglutinin is the primary surface glycoprotein of the influenza virus, mediating viral entry into host cells by binding to sialic acid receptors. Virus-like particles (VLPs) serve as a sophisticated delivery platform that mimics the structural organization of the native virus without containing infectious genetic material (Mohsen et al., 2017 [2]). When these VLPs display HA epitopes, they efficiently engage BCRs through multivalent binding, promoting robust B cell differentiation and the secretion of neutralizing antibodies (Sautto et al., 2018 [3]). Simultaneously, the processing of VLP-associated HA by antigen-presenting cells allows for the activation of TCRs, which provides the necessary signals for long-lived plasma cell formation and cellular immunity. This coordinated engagement of BCRs and TCRs is essential for developing broad-spectrum protection against seasonal and pandemic influenza strains. Therapeutic strategies focusing on these receptors often aim to target the conserved stalk region of the HA protein to elicit universal immunity (Krammer, 2019 [1]). By utilizing the VLP format, researchers can present these epitopes in a highly repetitive array that is particularly effective at triggering immune receptor signaling (Bright et al., 2007 [4]).

Other names

HA-specific immune receptorsHemagglutinin-reactive BCRs and TCRsInfluenza VLP-reactive receptorsHA-specific B-cell receptorsHA-specific T-cell receptors

VLP-based vaccines interact with BCRs by providing a multivalent display of HA epitopes, which induces receptor clustering and downstream signaling for B cell activation. These particles are also endocytosed by dendritic cells, where HA is proteolytically cleaved into peptides and loaded onto MHC molecules for recognition by TCRs, leading to T cell proliferation and cytokine production (Mohsen et al., 2017 [2]; Sautto et al., 2018 [3]).