Superantigen Recognition and Interactions: Functions, Mechanisms and Applications

Abstract

Superantigens are unconventional antigens which recognise immune receptors outside their usual recognition sites e.g. complementary determining regions (CDRs), to elicit a response within the target cell. T-cell superantigens crosslink T-cell receptors and MHC Class II molecules on antigen-presenting cells, leading to lymphocyte recruitment, induction of cytokine storms and T-cell anergy or apoptosis among many other effects. B-cell superantigens, on the other hand, bind immunoglobulins on B-cells, affecting opsonisation, IgG-mediated phagocytosis, and driving apoptosis. Here, through a review of the structural basis for recognition of immune receptors by superantigens, we show that their binding interfaces share specific physicochemical characteristics when compared with other protein-protein interaction complexes. Given that antibody-binding superantigens have been exploited extensively in industrial antibody purification, these observations could facilitate further protein engineering to optimize the use of superantigens in this and other areas of biotechnology.

Variable-heavy (VH) families influencing IgA1&2 engagement to the antigen, FcαRI and superantigen proteins G, A, and L

“…The microbial flora in mucosal areas 19 where IgA is commonly found, e.g. Staphylococcus aureus , secrete superantigens that bind antibodies 20 which prevents IgA-FcαRI interactions and serum killing of bacteria 21 , increasing susceptibility to septicemia (one of leading causes of death) 22 . These superantigens were also speculated to be linked to glomerulonephritis 23 , 24 , mimicking IgA nephropathy 25 , 26 , having clinical pathogenesis, thus requiring the engineering of future therapeutic IgAs resistance against such effects.…”

More Than Meets the Kappa for Antibody Superantigen Protein L (PpL)

“…B cell superantigens bind antibodies to hyperstimulate populations of B cells independent of T cells and have been widely used for antibody affinity purification [ 1 ]. Superantigens are predominantly produced by microorganisms as a defence mechanism to escape the host immune system [ 2 ].…”

Peering into Avian Influenza A(H5N8) for a Framework towards Pandemic Preparedness

“…This combinatorial approach of computational and experimental research has been previously applied in the COVID-19 pandemic, for both drug repurposing [128] and synergistic drug combinations [129]. Such knowledge, when coupled with antibody engineering [130], could also lead to development of better neutralizing antibodies, particularly if they are of mucosal antibodies of IgA [131] or even IgE [132,133], capable of recognizing superantigen elements [134] as the SARS-CoV-2 spike [135].…”