The self-peptide repertoire plays a critical role in transplant tolerance induction.

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From: Journal of Clinical Investigation(Vol. 131, Issue 21)
Publisher: American Society for Clinical Investigation
Document Type: Report
Length: 12,216 words
Lexile Measure: 1490L

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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.sup.+] T cells have not been defined. In this study, we used a combination of genetically engineered major histocompatibility complex class I (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 recognized pMHC epitopes and identified 17 strongly immunogenic H-2[K.sup.b]-associated peptides recognized by [CD8.sup.+] T cells from B10.BR (H-[2.sup.k]) mice, 13 of which were also recognized by BALB/c (H-[2.sup.d]) mice. As few as 5 different tetramers used together were able to identify a high proportion of alloreactive T cells within a polyclonal population, suggesting that there are immunodominant allogeneic MHC-peptide complexes that can account for a large component of the alloresponse.

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Gale Document Number: GALE|A682076196