A T-cell epitope encoded by a subset of HLA-DPB1 alleles determines nonpermissive mismatches for hematologic stem cell transplantation

Elisabetta Zino, Guido Frumento, Sarah Marktel, Maria Pia Sormani, Francesca Ficara, Simona Di Terlizzi, Anna Maria Parodi, Ruhena Sergeant, Miryam Martinetti, Andrea Bontadini, Francesca Bonifazi, Daniela Lisini, Benedetta Mazzi, Silvano Rossini, Paolo Servida, Fabio Ciceri, Chiara Bonini, Edoardo Lanino, Giuseppe Bandini, Franco Locatelli, Jane Apperley, Andrea Bacigalupo, Giovanni Battista Ferrara, Claudio Bordignon, Katharina Fleischhauer
Blood 2004 February 15, 103 (4): 1417-24
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.

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