title: Combined CD4 T-cell and antibody response to human minor histocompatibility antigen DBY after allogeneic stem-cell transplantation.
abstract: BACKGROUND
  Antibody responses to HY antigens in male recipients are frequent after transplantation of stem cells from female donors (Miklos et al., Blood 2005; 105: 2973; Miklos et al., Blood 2004; 103: 353). However, evidence that this B-cell immunity is accompanied by T-cell responses to the cognate antigens is scarce. Here, we examined T- and B-cell responses to DBY antigen in a male patient who received hematopoietic stem cells from a human leukocyte antigen-identical female sibling.
  
  
  METHODS
  We used 93 overlapping peptides representing the entire DBY protein to detect and characterize T-cell and antibody responses to DBY by enzyme-linked immunosorbent spot (ELISPOT) and enzyme-linked immunosorbent assay.
  
  
  RESULTS
  High frequency CD4+ T cells specific for a unique DBY peptide were detected in the patient blood. We isolated the corresponding T-cell clone and characterized the recognized epitope as an 18-mer peptide restricted by human leukocyte antigen-DRB1*0101. Upon stimulation, this clone produced cytokines with no evidence of Th1 or Th2 polarization. Remarkably, this clone also recognized the DBX homologue peptide and responded to female donor dendritic cells stimulated with poly I/C or lipopolysaccharide, indicating that the peptide was endogenously processed in these cells. High titer DBY-specific antibodies were also found in the patient serum which, in contrast to the T-cell response, did not cross-react with DBX.
  
  
  CONCLUSIONS
  We show here the development of a coordinated B and T-cell response to DBY in a recipient of sex mismatched allogeneic hematopoietic stem-cell transplantation. Our findings support a role for CD4+ T cells in the development of humoral immunity to minor histocompatibility antigens.
authors.affiliation: Department of Surgery, Transplant Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Porcheray
authors.forename: David B
authors.initials: DB
authors.lastname: Miklos
authors.forename: Blair H
authors.initials: BH
authors.lastname: Floyd
authors.forename: Stefanie
authors.initials: S
authors.lastname: Sarantopoulos
authors.forename: Roberto
authors.initials: R
authors.lastname: Bellucci
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Soiffer
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Antin
authors.forename: Edwin P
authors.initials: EP
authors.lastname: Alyea
authors.forename: Jerome
authors.initials: J
authors.lastname: Ritz
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Zorn
mesh_terms: D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D053487:DEAD-box RNA Helicases / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006650:Histocompatibility Testing; D006801:Humans; D007518:Isoantibodies / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens / Q000276:immunology*; D012737:Sex Factors; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D014184:Transplantation, Homologous
chemical_list: D016207:Cytokines; D007518:Isoantibodies; D015778:Minor Histocompatibility Antigens; C119332:DDX3X protein, human; C492034:DDX3Y protein, human; D053487:DEAD-box RNA Helicases