Intragraft selection of the T cell receptor repertoire by class I MHC sequences in tolerant recipients

Dahai Liu, Xiu Da Shen, Yuan Zhai, Wengsi Lam, Jingying Liao, Ronald W. Busuttil, Rafik M. Ghobrial

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Background: Allograft tolerance of ACI (RT1a) recipients to WF (RT1u) hearts can be induced by allochimeric class I MHC molecules containing donor-type (RT1Au) immunogenic epitopes displayed on recipient-type (RT1Aa) sequences. Here, we sought the mechanisms by which allochimeric sequences may affect responding T cells through T cell receptor (TCA) repertoire restriction. Methodology/Principal Findings: The soluble [α1h u]-RT1.Aa allochimeric molecule was delivered into ACI recipients of WF hearts in the presence of sub-therapeutic dose of cyclosporine (CsA). The TCR Vβ spectrotyping of the splenocytes and cardiac allografts showed that the Vβ gene families were differentially expressed within the TCR repertoire in allochimeric- or high-dose CsA-treated tolerant recipients at day +5 and +7 of post-transplantation. However, at day 30 of post-transplantation the allochimeric molecule-treated rats showed the restriction of TCR repertoire with altered dominant size peaks representing preferential clonal expansion of Vβ7, Vβ11, Vβ13, Vβ 14, and Vβ15 genes. Moreover, we found a positive correlation between the alteration of Vβ profile, restriction of TCR repertoire, and the establishment of allograft tolerance. Conclusions: Our findings indicate that presentation of allochimeric MHC class I sequences that partially mimic donor and recipient epitopes may induce unique tolerant state by selecting alloresponsive Vβ genes.

Original languageEnglish (US)
Article numbere6076
JournalPLoS ONE
Volume4
Issue number6
DOIs
StatePublished - Jun 29 2009

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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