Epitopes described in "Minor histocompatibility antigen DBY elicits a coordinated B and T cell response after allogeneic stem cell transplantation."

Article Authors:Emmanuel Zorn; David B Miklos; Blair H Floyd; Alex Mattes-Ritz; Luxuan Guo; Robert J Soiffer; Joseph H Antin; Jerome Ritz
Article Title:Minor histocompatibility antigen DBY elicits a coordinated B and T cell response after allogeneic stem cell transplantation.
Reference Detail
Reference ID:1020285
Abstract:We examined the immune response to DBY, a model H-Y minor histocompatibility antigen (mHA) in a male patient with chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplant from a human histocompatibility leukocyte antigen (HLA)-identical female sibling. Patient peripheral blood mononuclear cells were screened for reactivity against a panel of 93 peptides representing the entire amino acid sequence of DBY. This epitope screen revealed a high frequency CD4(+) T cell response to a single DBY peptide that persisted from 8 to 21 mo after transplant. A CD4(+) T cell clone displaying the same reactivity was established from posttransplant patient cells and used to characterize the T cell epitope as a 19-mer peptide starting at position 30 in the DBY sequence and restricted by HLA-DRB1*1501. Remarkably, the corresponding X homologue peptide was also recognized by donor T cells. Moreover, the T cell clone responded equally to mature HLA-DRB1*1501 male and female dendritic cells, indicating that both DBY and DBX peptides were endogenously processed. After transplant, the patient also developed antibodies that were specific for recombinant DBY protein and did not react with DBX. This antibody response was mapped to two DBY peptides beginning at positions 118 and 536. Corresponding DBX peptides were not recognized. These studies provide the first demonstration of a coordinated B and T cell immune response to an H-Y antigen after allogeneic transplant. The specificity for recipient male cells was mediated by the B cell response and not by donor T cells. This dual DBX/DBY antigen is the first mHA to be identified in the context of chronic GVHD.
Affiliations:Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney Street, M530, Boston, MA 02115, USA.
Reference Type:Literature
PubMed ID:15096539
Journal:J Exp Med
Journal Volume:199
Article Pages:1133-42
Journal ISSN:0022-1007
Article Chemical List:Epitopes;Isoantibodies;Minor Histocompatibility Antigens;Proteins;DDX3Y protein, human;DEAD-box RNA Helicases
Article MeSH List:Adult; Amino Acid Sequence; B-Lymphocytes(immunology); DEAD-box RNA Helicases; Epitopes(genetics); Female; Hematopoietic Stem Cell Transplantation; Humans; Isoantibodies(biosynthesis); Male; Minor Histocompatibility Antigens(genetics); Molecular Sequence Data; Proteins(genetics; immunology); T-Lymphocytes(immunology); Transplantation, Homologous
Curation Last Updated:2015-06-05 02:27:01