Antibody Blockade of MHC-I/Ly49 Interactions Enhances Humoral and Cellular Immunity

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B207
Abstract ID: 4901

Presenting Author:
Soha Kazmi , Post Baccalaureate at NIAID, NIH

Abstract:

Natural Killer (NK) cells are innate immune cells crucial to maintaining immune balance and initiating immune responses. In mice, NK cells recognize self-MHC-I via Ly-49 receptors that inhibit NK cell activation. We identified an anti-mouse pan MHC-I mAb (M1/42) that selectively disrupts the Ly-49/MHC-I interaction without blocking TCR binding sites on MHC-I. In vivo administration of M1/42 activates NK cells resulting in IFNg production leading to enhanced IL-12/15/18 production and MHC expression by antigen presenting cells. M1/42 treatment enhanced T cell memory responses in acute LCMV infection, inhibited tumor growth and restricted liver and lung metastases by promoting the infiltration and expansion of antigen-specific CD8 T cells in the tumor microenvironment. We evaluated the potential adjuvant effects of M1/42 treatment using a soluble OVA-immunization model. Mice were immunized twice with OVA in CFA or soluble OVA alone. Anti-OVA IgG titers were measured in serum after 30 days and were two-fold higher (4mg/ml vs 2mg/ml) in animals that received OVA and M1/42 compared to OVA alone. The total number of antigen-specific CD8 T cells was 20-fold higher in the OVA and M1/42 immunized mice than mice that received OVA alone. OVA-M1/42 immunization generated 2-fold higher antigen-specific T cells compared to OVA in CFA. Our findings suggest that anti-MHC-I blockade of MHC-I/Ly-49 interactions may represent a novel adjuvant capable of enhancing humoral and cellular immunity.