13 research outputs found
Lipid Motif of a Bacterial Antigen Mediates Immune Responses via TLR2 Signaling
The cross-talk between the innate and the adaptive immune system is facilitated
by the initial interaction of antigen with dendritic cells. As DCs express a
large array of TLRs, evidence has accumulated that engagement of these molecules
contributes to the activation of adaptive immunity. We have evaluated the
immunostimulatory role of the highly-conserved outer membrane lipoprotein P6
from non-typeable Haemophilus influenzae (NTHI) to determine
whether the presence of the lipid motif plays a critical role on its
immunogenicity. We undertook a systematic analysis of the role that the lipid
motif plays in the activation of DCs and the subsequent stimulation of
antigen-specific T and B cells. To facilitate our studies, recombinant P6
protein that lacked the lipid motif was generated. Mice immunized with
non-lipidated rP6 were unable to elicit high titers of anti-P6 Ig. Expression of
the lipid motif on P6 was also required for proliferation and cytokine secretion
by antigen-specific T cells. Upregulation of T cell costimulatory molecules was
abrogated in DCs exposed to non-lipidated rP6 and in
TLR2−/− DCs exposed to native P6, thereby resulting
in diminished adaptive immune responses. Absence of either the lipid motif on
the antigen or TLR2 expression resulted in diminished cytokine production from
stimulated DCs. Collectively; our data suggest that the lipid motif of the
lipoprotein antigen is essential for triggering TLR2 signaling and effective
stimulation of APCs. Our studies establish the pivotal role of a bacterial lipid
motif on activating both innate and adaptive immune responses to an otherwise
poorly immunogenic protein antigen