CagL is an essential pilus surface component of the virulence-associated type IV secretion system (T4SS) employed by Helicobacter pylori to translocate the oncogenic effector protein CagA into human gastric epithelial cells. CagL contains an RGD motif and integrin α₅ β₁ is widely accepted as its host cell receptor. Here, we show that CagL binds integrin α_V β₆ with substantially higher affinity and that this interaction is functionally important. Cell surface expression of α_V β₆ on various cell lines correlated perfectly with cell adhesion to immobilized CagL and with binding of soluble CagL to cells. We found no such correlation for α₅ β₁ . The purified α_V β₆ ectodomain bound CagL with high affinity. This interaction was highly specific, as the affinity of CagL for other RGD-binding integrins was two to three orders of magnitude weaker. Mutation of either conserved leucine in the CagL RGDLXXL motif, a motif that generally confers specificity for integrin α_V β₆ and α_V β₈ , lowered the affinity of CagL for α_V β₆ . Stable expression of α_V β₆ in α_V β₆ -negative but α₅ β₁ -expressing human cells promoted two hallmarks of the functional H. pylori T4SS, namely translocation of CagA into host cells and induction of interleukin-8 secretion by host cells. These findings suggest that integrin α_V β₆ , although not essential for T4SS function, represents an important host cell receptor for CagL.

Maren Buß

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