A T-cell epitope encoded by a subset of HLA-DPB1 alleles determines nonpermissive mismatches for hematologic stem cell transplantation.
The importance of HLA-DPB1 matching for the outcome of allogeneic hematologic stem cell (HSC) transplantation is controversial. We have previously identified HLA-DPB1*0901 as a target of cytotoxic T cells mediating in vivo rejection of an HSC allograft. Here we show that HLA-DPB1*0901 encodes a T-cell epitope shared by a subset of DPB1 alleles that determines nonpermissive mismatches for HSC transplantation. Several T-cell clones obtained from the patient at the time of rejection showed HLA-DP restricted recognition of allogeneic targets expressing HLA-DPB1*0901, *1001, *1701, *0301, *1401, and *4501, but not other alleles. Based on these findings, we developed an algorithm for prediction of nonpermissive HLA-DPB1 mismatches. Retrospective evaluation of 118 transplantations showed that the presence of nonpermissive HLA-DPB1 mismatches was correlated with significantly increased hazards of acute grade II to IV graft-versus-host disease (HR = 1.87, P =.046) and transplantation-related mortality (HR = 2.69, P =.027) but not relapse (HR = 0.98, P =.939), as compared with the permissive group. There was also a marked but statistically not significant increase in the hazards of overall mortality (HR = 1.64, P =.1). These data suggest that biologic characterization of in vivo alloreactivity can be a tool for definition of clinically relevant nonpermissive HLA mismatches for unrelated HSC transplantation.
Zino
Elisabetta
E
HLA Tissue Typing Laboratory, Immunohematology and Transfusion Medicine Service, San Raffaele Telethon Institue for Gene Therapy, Cancer Immunotherapy and Gene Therapy Program, Istituto Scientifico H. S. Raffaele, via Olgettina 60, I-20132 Milan, Italy.
Frumento
Guido
G
Marktel
Sarah
S
Sormani
Maria Pia
MP
Ficara
Francesca
F
Di Terlizzi
Simona
S
Parodi
Anna Maria
AM
Sergeant
Ruhena
R
Martinetti
Miryam
M
Bontadini
Andrea
A
Bonifazi
Francesca
F
Lisini
Daniela
D
Mazzi
Benedetta
B
Rossini
Silvano
S
Servida
Paolo
P
Ciceri
Fabio
F
Bonini
Chiara
C
Lanino
Edoardo
E
Bandini
Giuseppe
G
Locatelli
Franco
F
Apperley
Jane
J
Bacigalupo
Andrea
A
Ferrara
Giovanni Battista
GB
Bordignon
Claudio
C
Fleischhauer
Katharina
K
D000465:Algorithms; D000483:Alleles; D000595:Amino Acid Sequence; D003429:Cross Reactions; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D006086:Graft vs Host Disease / Q000276:immunology; D006682:HLA-DP Antigens / Q000235:genetics / Q000276:immunology*; D059868:HLA-DP beta-Chains; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007519:Isoantigens / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; D007519:Isoantigens