A peptide presentation by an MHC tetramer reduces the expansion of the peptide-specific T cells and the reduced expansion is reversible by PD-1 blockades

Abstract

Abstract Background Peptide-MHC (pMHC) tetramers have been widely used in infectious disease and immune-oncology area to detect antigen-specific T cells. However, little is reported about their application in the context of pMHC presentation to stimulate T cells. Here we compared the expansion of antigen-specific T cells stimulated by an unlabeled pMHC tetramer and the peptide. We also analyzed the relationship among the programmed death-1 (PD-1), lymphocyte activation gene-3 (LAG-3), PD-L1, CD80 and CD38 expression on antigen-specific and non-specific T cells. Results Compared to the peptide stimulation, the pMHC tetramer induced lower expansion of the peptide-specific T cells. PD-1, PD-L1, CD80, and LAG3 expression was significantly higher on peptide-specific T cells than on non-specific T cells. Interestingly, peptide-specific T cells expanded by pMHC tetramer induced lower numbers of dysfunctional PD-1+CD38high CD8+ T cells. Furthermore, blockade of the PD-1 pathway by using an FDA approved antibody reversed such a restriction of expansion. Conclusion The pMHC tetramer stimulation resulted in the reduced expansion of peptide-specific CD8 T cells when compared to the peptide stimulation. Since the impaired expansion was reversed by the anti-PD1 therapeutic antibody, this artificial stimulation method could be used as a functional in vitro immune-oncology drug screening tool.