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The Staphylococcus aureus Cell Wall-Anchored Protein Clumping Factor A Is an Important T Cell Antigen.

The Staphylococcus aureus Cell Wall-Anchored Protein Clumping Factor A Is an Important T Cell Antigen.
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Lacey KA, Leech JM, Lalor SJ, McCormack N, Geoghegan JA, McLoughlin RM,


Lacey KA, Leech JM, Lalor SJ, McCormack N, Geoghegan JA, McLoughlin RM, (click to view)

Lacey KA, Leech JM, Lalor SJ, McCormack N, Geoghegan JA, McLoughlin RM,

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Infection and immunity 2017 11 1785(12) pii 10.1128/IAI.00549-17

Abstract

Staphylococcus aureus has become increasingly resistant to antibiotics, and vaccines offer a potential solution to this epidemic of antimicrobial resistance. Targeting of specific T cell subsets is now considered crucial for next-generation anti-S. aureus vaccines; however, there is a paucity of information regarding T cell antigens of S. aureus This study highlights the importance of cell wall-anchored proteins as human CD4+ T cell activators capable of driving antigen-specific Th1 and Th17 cell activation. Clumping factor A (ClfA), which contains N1, N2, and N3 binding domains, was found to be a potent human T cell activator. We further investigated which subdomains of ClfA were involved in T cell activation and found that the full-length ClfA N123 and N23 were potent Th1 and Th17 activators. Interestingly, the N1 subdomain was capable of exclusively activating Th1 cells. Furthermore, when these subdomains were used in a model vaccine, N23 and N1 offered Th1- and Th17-mediated systemic protection in mice upon intraperitoneal challenge. Overall, however, full-length ClfA N123 is required for maximal protection both locally and systemically.

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