Research paperStimulation of HIV-specific T cell clonotypes using allogeneic HLA

- HIV-specific T cell clones were tested for crossreactivity against allogeneic HLA.
- HIV-specific T cells can frequently be stimulated using allogeneic HLA molecules.
- Allo-HLA crossreactivity is specific to the TRBV usage of the HIV-specific T cells.
- Allo-HLA stimulation is likely also dependent on endogenous peptide presentation.

We hypothesized that HIV-specific CD8 T cell clonotypes can be stimulated by allogeneic HLA molecules. Multiple HIV-specific CD8 T cell clones were derived from 12 individuals with chronic HIV infection, specific for 13 different HIV Gag antigens and restricted to 7 different HLA molecules. The generated T cell clones were assayed for alloreactivity against a panel of single HLA class I expressing cell lines (SALs). HIV-specific T cells recognising at least one allogeneic HLA molecule could be identified from 7 of 12 patients tested. Allorecognition was associated with IFNγ cytokine production, CD137 upregulation and cytotoxicity, suggesting high avidity allo-stimulation. Allo-HLA recognition by HIV-specific T cells was specific to the HIV target peptide/HLA restriction and TCR TRBV usage of the T cells. HIV-specific T cells do crossreact against allogeneic HLA molecules in an epitope and TRBV specific manner. Therefore allo-HLA stimulation could be exploited to induce or augment HIV-specific T cell responses.