Allo-HLA reactivity by HIV-specific T cells: A potential adjunct to HIV vaccine design

The rate of new HIV infections continues to be high, particularly in the developing world. An effective preventative HIV vaccine remains elusive and therefore novel vaccine strategies are urgently required. We have recently reported that allo-HLA crossreactivity by EBV, CMV, VZV and influenza virus-specific T cells is common, and that specific allo-HLA stimulation can conversely be used to augment a virus-specific T cell response. We hypothesized that HIV-specific T cells can be stimulated by allogeneic HLA molecules.

Multiple HIV-1 specific CD8 T cell clones were generated using single cell sorting based on HIV peptide/HLA tetrameric complex staining. The generated T cell clones were assayed for allo-reactivity against a panel of cell lines expressing single HLA molecules (SALs) by measuring CD137 expression and cytotoxicity by flow cytometry and IFNγ production by ELISA.

We identified a number of HIV-specific CD8 T cells that cross-reacted with allo-HLA molecules. Allo-HLA reactivity was specific to the HIV epitope/HLA-restriction and Vβ usage of the T cells. In all we identified 11 HLA-epitope combinations from eight individuals that responded to various allo-HLA molecules. Additionally, two HIV-specific T cell clones showed reactivity against two allo-HLA molecules.

HIV-specific T cells crossreact against allogeneic HLA molecules, and therefore allo-HLA stimulation could be a useful adjunct to HIV vaccine design. 

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