Localization of cryptic tolerogenic epitopes in the alpha1-helical region of the RT1.Au alloantigen

Transplantation
M WangB D Kahan

Abstract

Transplantation tolerance is induced by perioperative administration of host class I major histocompatibility complex proteins bearing donor-type amino acid (a.a.) epitopes substituted for native residues. Herein we demonstrate that two cryptic tolerogenic a.a. epitopes are localized in the alpha1-helical region of the rat RT1.Au class I major histocompatibility complex alloantigen. Three allochimeric proteins were produced by superimposing the nucleotides encoding donor-type RT1.Au a.a. onto the host RT1.Aa backbone using the polymerase chain reaction-based method of gene splicing with overlap extension. We substituted nucleotide sequences encoding all nine (Arg62, Glu63, Gln65, Gly66, Gly69, His70, Val73, Asn74, and Asn77; alpha1h u62-77-RT1.Aa), the first four (Arg62, Glu63, Gln65, and Gly69; alpha1h u62-69-RT1.Aa), or the last four (His70, Val73, Asn74, and Asn77; alpha1h u70-77-RT1.Aa) alpha1-helical RT1.Au polymorphic a.a. in RT1.Aa cDNA. A baculovirus/Spodoptera frugiperda (Sf9) expression system was harnessed for production of the proteins. Untreated ACI (RT1a) rats reject Wistar-Furth (WF; RT1u) heart allografts at a mean survival time of 8.9+/-1.0 days. A single portal vein injection of 10 microg of alpha1h u62-77-RT1...Continue Reading

References

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Citations

Mar 27, 2001·Transplantation Proceedings·M WangB D Kahan
Dec 26, 2001·Transplantation Proceedings·S M StepkowskiR A Kirken
Dec 26, 2001·Transplantation Proceedings·G J PettigrewJ A Bradley
Dec 26, 2001·Transplantation Proceedings·S M StepkowskiR A Kirken
Dec 26, 2001·Transplantation Proceedings·S M StepkowskiB D Kahan
Oct 8, 2003·Transplantation Proceedings·B D Kahan
Sep 2, 1998·Transplantation Proceedings·C C Magee, M H Sayegh
May 20, 1999·Transplantation Proceedings·M WangB D Kahan
Nov 22, 1997·Current Opinion in Immunology·C C Magee, M H Sayegh
Oct 15, 2011·Transplantation Proceedings·B D Kahan
Nov 21, 2007·Cellular Immunology·Ankit Bharat, T Mohanakumar
Jul 15, 2004·Transplantation Proceedings·K Praditpornsilpa, Y Avihingsanon
Oct 3, 2003·Nature Reviews. Immunology·Barry D Kahan
Jun 11, 1999·Journal of the American Society of Nephrology : JASN·B Murphy, A M Krensky

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