title: Identification of epitopes and immunodominant regions on the MICA protein defined by alloantibodies from kidney transplant patients.
abstract: BACKGROUND
  Several reports showed a contribution of anti-MICA (major histocompatibility complex class I chain-related molecule A) antibodies (Abs) to the development of acute and chronic rejection. Identification of the epitopes to which the Abs bind may help to determine immunoreactive regions essential for the major histocompatibility complex compatibility between donor and recipients, leading to the best outcome of the transplant.
  
  
  METHODS
  Sera from 284 kidney transplant patients were screened for anti-MICA Abs by Luminex assay. MICA allele typing of the recipients was determined. The epitopes of MICA were mapped by screening a synthesized library of overlapping peptides from the extracellular domains of the protein against the sera from kidney transplant patients with anti-MICA Abs.
  
  
  RESULTS
  Antibodies against MICA were detected in 50 of 284 patients (17.6%) and correlated with the development of acute rejection. Nine antigenic regions were immunoreactive with anti-MICA Abs in the sera samples. Four of these continuous epitopes mapped to polymorphic amino acids (aa). Five antigenic regions were shared epitopes found in all the MICA alleles. The polymorphic residues, 173 (E/K), 175 (S/G), and 181 (R/T), had determined allele-specific epitopes (reactivity patterns 1 and 2). In contrast, the aa 208Y and 213T were implicated in the cross-reactivity among alleles.
  
  
  CONCLUSIONS
  The presence of anti-MICA Abs could be an important marker for diagnosis because of their contribution to the outcome of the graft, regardless of presence of anti-HLA Abs. Additionally, the identification of epitopes revealed the in vivo antigens of the transplant and is spurring the development of new matching strategies to reduce the incidence of acute and chronic rejection.
authors: Department of Immunology, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors: Beatriz
authors: B
authors: Suárez-Alvarez
authors: Rebeca
authors: R
authors: Alonso-Arias
authors: Cristina
authors: C
authors: Bravo-Mendoza
authors: Antonio
authors: A
authors: López-Vázquez
authors: Teresa
authors: T
authors: Ortega
authors: Jose Maria
authors: JM
authors: Baltar
authors: Eliecer
authors: E
authors: Coto
authors: Francisco
authors: F
authors: Ortega
authors: Carlos
authors: C
authors: López-Larrea
mesh_terms: D000368:Aged; D000906:Antibodies / Q000276:immunology; D042783:Endothelial Cells / Q000276:immunology; D000939:Epitopes / Q000032:analysis*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006650:Histocompatibility Testing / Q000379:methods; D006801:Humans; D016056:Immunodominant Epitopes / Q000032:analysis*; D015994:Incidence; D007518:Isoantibodies / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012086:Reoperation / Q000706:statistics & numerical data; D012189:Retrospective Studies; D017211:Treatment Failure
chemical_list: D000906:Antibodies; D000939:Epitopes; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D016056:Immunodominant Epitopes; D007518:Isoantibodies; C099187:MHC class I-related chain A