T-cell receptor specific for Agglutinin-like sequence 3 (Als3-specific TCR)

T-cell receptors (TCRs) specific for the Agglutinin-like sequence 3 (Als3) antigen are the primary mediators of adaptive cellular immunity against Candida albicans. Als3 is a multifunctional cell-surface adhesin and invasin that is essential for the fungal pathogen's ability to form biofilms and invade host cells (Uppuluri et al., 2017). These TCRs recognize Als3-derived peptides presented by MHC Class II molecules, triggering the differentiation of CD4+ T-cells into Th1 and Th17 subsets (Schmidt et al., 2012). This activation leads to the secretion of critical cytokines, including interferon-gamma (IFN-gamma) and interleukin-17A (IL-17A), which enhance the microbicidal activity of neutrophils and macrophages (Edwards et al., 2018). The therapeutic targeting of Als3-specific TCRs is most notably achieved through the NDV-3A vaccine, which utilizes a recombinant N-terminal portion of the Als3 protein (rAls3p-N) to prime the immune system. Clinical studies have demonstrated that inducing these specific TCR responses can protect against recurrent vulvovaginal candidiasis and potentially invasive candidiasis (Edwards et al., 2018). Furthermore, Als3-specific TCRs exhibit cross-reactivity with surface proteins of Staphylococcus aureus, such as clumping factor A (ClfA), providing a unique mechanism for cross-kingdom vaccine protection (Ibrahim et al., 2013).

Other names

Als3-specific T-cell receptorAgglutinin-like sequence 3-specific TCRrAls3p-N-specific TCR

Activation of Th1 and Th17 cells via TCR recognition of Als3 peptides, leading to IFN-gamma and IL-17A production.