OR24 Allo-HLA reactivity by HIV-specific T-cells: A potential adjunct to HIV vaccine design?

Aim 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 also 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. Methods 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 alloreactivity against a panel of single HLA expressing cell lines (SALs), using cytokine assay, CD137 upregulation and cytotoxicity as readout. Results HIV-specific T cells do crossreact against allogeneic HLA molecules. For example, a HIV Gag RK9/HLA-A3 specific T cell clone with TCR Vb23 recognised allogeneic HLA-A*69:01. A HIV Gag KK10/HLA-B27 specific T cell clone with TCR Vb5.1 usage recognized allogeneic HLA-A*33:03 and HLA-B*57:01. A HIV Gag KF11/HLA-B57 specific T cell clone with Vb17 usage recognized allogeneic HLA-B*44:02. Allo-HLA reactivity by HIV-specific T cells was specific to the HIV target peptide/HLA restriction and Vb usage of the T cells. Overall 7/39 HIV-specific T cell clones tested could be stimulated by at least one allogeneic HLA molecule. Conclusion HIV-specific T cells do crossreact against allogeneic HLA molecules, and therefore allo-HLA stimulation could be a useful adjunct to HIV vaccine design. Download full-size image