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Toxins 2014, 6(2), 556-574; doi:10.3390/toxins6020556
Review

Soluble T Cell Receptor Vβ Domains Engineered for High-Affinity Binding to Staphylococcal or Streptococcal Superantigens

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Received: 16 December 2013; in revised form: 21 January 2014 / Accepted: 22 January 2014 / Published: 28 January 2014
(This article belongs to the Special Issue Enterotoxins: Microbial Proteins and Host Cell Dysregulation)
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Abstract: Staphylococcus aureus and group A Streptococcus secrete a collection of toxins called superantigens (SAgs), so-called because they stimulate a large fraction of an individual’s T cells. One consequence of this hyperactivity is massive cytokine release leading to severe tissue inflammation and, in some cases, systemic organ failure and death. The molecular basis of action involves the binding of the SAg to both a T cell receptor (TCR) on a T cell and a class II product of the major histocompatibility complex (MHC) on an antigen presenting cell. This cross-linking leads to aggregation of the TCR complex and signaling. A common feature of SAgs is that they bind with relatively low affinity to the variable region (V) of the beta chain of the TCR. Despite this low affinity binding, SAgs are very potent, as each T cell requires only a small fraction of their receptors to be bound in order to trigger cytokine release. To develop high-affinity agents that could neutralize the activity of SAgs, and facilitate the development of detection assays, soluble forms of the Vβ regions have been engineered to affinities that are up to 3 million-fold higher for the SAg. Over the past decade, six different Vβ regions against SAgs from S. aureus (SEA, SEB, SEC3, TSST-1) or S. pyogenes (SpeA and SpeC) have been engineered for high-affinity using yeast display and directed evolution. Here we review the engineering of these high-affinity Vβ proteins, structural features of the six different SAgs and the Vβ proteins, and the specific properties of the engineered Vβ regions that confer high-affinity and specificity for their SAg ligands.
Keywords: superantigens; yeast display; directed evolution; affinity maturation; T-cell receptor; complementarity determining regions; framework regions superantigens; yeast display; directed evolution; affinity maturation; T-cell receptor; complementarity determining regions; framework regions
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Sharma, P.; Wang, N.; Kranz, D.M. Soluble T Cell Receptor Vβ Domains Engineered for High-Affinity Binding to Staphylococcal or Streptococcal Superantigens. Toxins 2014, 6, 556-574.

AMA Style

Sharma P, Wang N, Kranz DM. Soluble T Cell Receptor Vβ Domains Engineered for High-Affinity Binding to Staphylococcal or Streptococcal Superantigens. Toxins. 2014; 6(2):556-574.

Chicago/Turabian Style

Sharma, Preeti; Wang, Ningyan; Kranz, David M. 2014. "Soluble T Cell Receptor Vβ Domains Engineered for High-Affinity Binding to Staphylococcal or Streptococcal Superantigens." Toxins 6, no. 2: 556-574.


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