The self-peptide repertoire plays a critical role in transplant tolerance induction
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ABSTRACT: While direct allorecognition underpins both solid organ allograft rejection and tolerance induction, the specific molecular targets of most directly-alloreactive CD8+ T cells have not been defined. In this study, we used a combination of genetically-engineered MHC I constructs, mice with a hepatocyte-specific mutation in the class I antigen-presentation pathway and immunopeptidomic analysis to provide definitive evidence for the contribution of the peptide cargo of allogeneic MHC I molecules to transplant tolerance induction. We established a systematic approach for the discovery of directly-recognised pMHC epitopes, and identified 17 strongly immunogenic H-2Kb-associated peptides recognised by CD8+ T cells from B10.BR (H-2k) mice, 13 of which were also recognised by BALB/c (H-2d) mice. As few as five different tetramers used together were able to identify almost 40% of alloreactive T cells within a polyclonal population. To our knowledge, this represents the first example of such an approach in the context of direct allorecognition.
INSTRUMENT(S): Q Exactive
ORGANISM(S): Mus Musculus (mouse)
TISSUE(S): Spleen, Liver, Skin
SUBMITTER: Pouya Faridi
LAB HEAD: Anthony Purcell
PROVIDER: PXD022695 | Pride | 2021-12-06
REPOSITORIES: Pride
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