Immunogenicity of the ??1-Helical Region of Rat RT1.A Class I MHC Antigens

Reemtsen, Brian; Zhai, Yuan; Wang, M.; Stepkowski, S.; Kahan, Barry D.; Busuttil, Ronald W.; Kupiec‐Weglinski, Jerzy W.; Ghobrial, Rafik M.

doi:10.1097/00007890-199905150-00143

Cited by 1 publication

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previously we have mapped an immunogenic determinant for rat class I RT1 u , RT1 l and RT1 a alloantigens to amino acid residues 58–80 on α 1 -helical polymorphic region [20], [21]. MHC alloantigens are therefore similar to multideterminant protein antigens that bear localized immunodominant amino acid sequences that trigger immune responses toward the whole protein molecule [22]–[25].…”

Section: Introductionmentioning

confidence: 99%

Intragraft Selection of the T Cell Receptor Repertoire by Class I MHC Sequences in Tolerant Recipients

et al. 2009

View full text Add to dashboard Cite

BackgroundAllograft 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 FindingsThe 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.ConclusionsOur 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.

show abstract