title: Acute graft versus host disease due to T lymphocytes recognizing a single HLA-DPB1*0501 mismatch.
abstract: Analysis of a large number of unrelated bone marrow transplantations (BMT) has shown that HLA-DP incompatibility did not detectably influence the risk for acute graft-versus-host disease (aGVHD). Accordingly, it was proposed that HLA-DP determinants did not function as transplantation antigens in the same way as HLA-A, -B, or -DR. We have previously shown that HLA-DP (as well as HLA-A, -B, -DQ, or -DR)-specific T cells could be isolated from skin biopsies of patients who developed an aGVHD after semiallogeneic BMT. Nevertheless, whether a single HLA-DP mismatched allele could induce a detectable allo-specific reaction in vivo after BMT remained to be established. To directly address this issue we studied one patient who presented aGVHD after receiving purified CD34+ bone marrow (BM) cells from an unrelated donor with a single HLA-DP mismatch in the GVHD direction. To characterize the immunological events associated with GVHD, we analyzed the peripheral T cell repertoire, the T cell receptor Vbeta diversity, and the specificity of T cells invading a skin biopsy at the onset of GVHD. Our results demonstrated that a large fraction of skin-infiltrating lymphocytes, which expressed diverse T cell receptors, were reactive against this single HLA-DPB1 *0501 mismatch and consequently that a single HLA-DP mismatch between BM donor and recipient can activate a strong T cell response in vivo.
authors.affiliation: Insitut National de la Santé et de Recherche Médicale, Plateau Technique du CHR, Mantes, France.
authors.forename: J
authors.initials: J
authors.lastname: Gaschet
authors.forename: A
authors.initials: A
authors.lastname: Lim
authors.forename: L
authors.initials: L
authors.lastname: Liem
authors.forename: R
authors.initials: R
authors.lastname: Vivien
authors.forename: M M
authors.initials: MM
authors.lastname: Hallet
authors.forename: J L
authors.initials: JL
authors.lastname: Harousseau
authors.forename: J
authors.initials: J
authors.lastname: Even
authors.forename: E
authors.initials: E
authors.lastname: Goulmy
authors.forename: M
authors.initials: M
authors.lastname: Bonneville
authors.forename: N
authors.initials: N
authors.lastname: Milpied
authors.forename: H
authors.initials: H
authors.lastname: Vié
mesh_terms: D000483:Alleles; D015703:Antigens, CD / Q000032:analysis; D001483:Base Sequence; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002465:Cell Movement; D002999:Clone Cells / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology*; D006682:HLA-DP Antigens / Q000276:immunology*; D059868:HLA-DP beta-Chains; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy*; D008875:Middle Aged; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta