Potentiating functional antigen-specific CD8? T cell immunity by a novel PD1 isoform-based fusion DNA vaccine.

ABSTRACT: Understanding and identifying new ways of mounting an effective CD8? T cell immune response is important for eliminating infectious pathogens. Although upregulated programmed death-1 (PD1) in chronic infections (such as HIV-1 and tuberculosis) impedes T cell responses, blocking this PD1/PD-L pathway could functionally rescue the "exhausted" T cells. However, there exists a number of PD1 spliced variants with unknown biological function. Here, we identified a new isoform of human PD1 (?42PD1) that contains a 42-nucleotide in-frame deletion located at exon 2 domain found expressed in peripheral blood mononuclear cells (PBMCs). ?42PD1 appears to function distinctly from PD1, as it does not engage PD-L1/PD-L2 but its recombinant form could induce proinflammatory cytokines. We utilized ?42PD1 as an intramolecular adjuvant to develop a fusion DNA vaccine with HIV-1 Gag p24 antigen to immunize mice, which elicited a significantly enhanced level of anti-p24 IgG1/IgG2a antibody titers, and important p24-specific and tetramer?CD8? T cells responses that lasted for ?7.5 months. Furthermore, p24-specific CD8? T cells remain functionally improved in proliferative and cytolytic capacities. Importantly, the enhanced antigen-specific immunity protected mice against pathogenic viral challenge and tumor growth. Thus, this newly identified PD1 variant (?42PD1) amplifies the generation of antigen-specific CD8? T cell immunity when used in a DNA vaccine.

SUBMITTER: Zhou J 

PROVIDER: S-EPMC3702111 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature