title: T Lymphocyte responses to nonpolymorphic HLA-derived peptides are associated with chronic renal allograft dysfunction.
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.
  
  
  CONCLUSIONS
  These findings suggest a strategy for assessing cellular immune responses to transplantation antigens with potential for generalization.
authors.affiliation: Department of Renal Medicine, Queen Elizabeth Hospital Birmingham, Edgbaston, Birmingham, United Kingdom.
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Smith
authors.forename: Rajesh
authors.initials: R
authors.lastname: Hanvesakul
authors.forename: Andrew
authors.initials: A
authors.lastname: Bentall
authors.forename: Shazia
authors.initials: S
authors.lastname: Shabir
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Morgan
authors.forename: David
authors.initials: D
authors.lastname: Briggs
authors.forename: Paul
authors.initials: P
authors.lastname: Cockwell
authors.forename: Richard
authors.initials: R
authors.lastname: Borrows
authors.forename: Mark
authors.initials: M
authors.lastname: Larché
authors.forename: Simon
authors.initials: S
authors.lastname: Ball
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D058501:Enzyme-Linked Immunospot Assay; D000939:Epitopes / Q000235:genetics; D005260:Female; D006084:Graft Rejection / Q000378:metabolism* / Q000473:pathology; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007371:Interferon-gamma / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism; D016030:Kidney Transplantation / Q000473:pathology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000494:pharmacology*; D051437:Renal Insufficiency / Q000601:surgery; D014184:Transplantation, Homologous
chemical_list: D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit; D010455:Peptides; D007371:Interferon-gamma