Neisserial Porins and Antigen Presenting Cells

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DESCRIPTION (provided by applicant): Neisserial porins (gonococcal Protein I [PIA or PIB] or meningococcal class 1 [PorA], 2 or 3 [PorB] proteins) are the major protein constituent of the Neisserial outer membrane. They have significant homology in structure and function amongst themselves and other Gram-negative porins. These porins have been shown to be potent immune adjuvants and we have demonstrated that this related to their ability to activate antigen presenting cells (APC), and upregulate the expression of the costimulatory molecule CD86 and class II MHC. During the last cycle of this proposal, we have shown that this effect of porins, specifically PorB, on APC is mediated by recognition of PorB by the pattern recognition receptor TLR2 and is MyD88 and TIRAP dependent. The goals of this current proposal are three-fold, 1) Demonstrate the direct interaction of porin PorB with TLR2, 2) determine which TLR2 co-receptor, TLR1 or TLR6 is involved in PorB induced TLR2 mediated activity and 3) determine which APC are essential for porin adjuvant activity and the relationship of this activity to APC antigen presentation and TLR2 activation. The fulfillment of these aims will greatly enhance our knowledge regarding bacterial component interaction with TLRs and the role of TLRs and APC in immune responses.