T lymphocyte responses to nonpolymorphic HLA-derived peptides are associated with chronic renal allograft dysfunction

Helen J. Smith, Rajesh Hanvesakul, Andrew Bentall, Shazia Shabir, Matthew D. Morgan, David Briggs, Paul Cockwell, Richard Borrows, Mark Larché, Simon Ball

Research output: Contribution to journalReview article

8 Scopus citations

Abstract

Background: The routine assessment of cellular alloimmunity to guide therapy is of perennial interest because this limb of the immune system is the main target of current transplant immunosuppression. That this has not as yet been realized in clinical practice reflects the difficulty of developing a standardized assay that accounts for the high degree of polymorphism exhibited by histocompatibility antigens. Methods: We have investigated whether immune responses to peptides derived from nonpolymorphic regions of human leukocyte antigen arise after transplantation, in particular in those with chronic allograft dysfunction. Results: Peripheral blood mononuclear cell γ-interferon production to peptides derived from the nonpolymorphic α3 domain of class 1 human leukocyte antigen occurred more frequently in long-term renal transplant recipients than healthy controls (51/110 vs. 1/18, 46.3% vs. 5.5%; P<0.001). These responses were associated with chronic allograft dysfunction manifested by a reduced and decreasing estimated glomerular filtration rate (responders vs. nonresponders: 39.5 vs. 48.8 mL/min, P=0.015 and -4.1 vs. -1.3 mL/min/year, P=0.008). Responses occurred mostly to autologous, "cryptic self-epitopes" and arose from CD4CD25CD127 T lymphocytes, which have been previously implicated in chronic rejection. Conclusion: These findings suggest a strategy for assessing cellular immune responses to transplantation antigens with potential for generalization.

Original languageEnglish (US)
Pages (from-to)279-286
Number of pages8
JournalTransplantation
Volume91
Issue number3
DOIs
StatePublished - Feb 15 2011

Keywords

  • Autologous peptides
  • Chronic allograft dysfunction
  • HLA

ASJC Scopus subject areas

  • Transplantation

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    Smith, H. J., Hanvesakul, R., Bentall, A., Shabir, S., Morgan, M. D., Briggs, D., Cockwell, P., Borrows, R., Larché, M., & Ball, S. (2011). T lymphocyte responses to nonpolymorphic HLA-derived peptides are associated with chronic renal allograft dysfunction. Transplantation, 91(3), 279-286. https://doi.org/10.1097/TP.0b013e318203862d