Superantigen Recognition and Interactions: Functions, Mechanisms and Applications

Front Immunol. 2021 Sep 20;12:731845. doi: 10.3389/fimmu.2021.731845. eCollection 2021.


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.

Keywords: B-cell; T-cell; antibody purification; cytokine storm; interface; superantigen.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antibodies / isolation & purification
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism*
  • Apoptosis
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism*
  • B-Lymphocytes / pathology
  • Clonal Anergy
  • Cytokine Release Syndrome / immunology
  • Cytokine Release Syndrome / metabolism
  • Histocompatibility Antigens Class II / immunology
  • Histocompatibility Antigens Class II / metabolism*
  • Humans
  • Immunoglobulin Fragments / immunology
  • Immunoglobulin Fragments / metabolism*
  • Lymphocyte Activation*
  • Protein Engineering
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism*
  • Signal Transduction
  • Superantigens / immunology
  • Superantigens / metabolism*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / pathology


  • Antibodies
  • Histocompatibility Antigens Class II
  • Immunoglobulin Fragments
  • Receptors, Antigen, T-Cell
  • Superantigens