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

Elisabetta E Zino, Guido G Frumento, Sarah S Marktel, Maria Pia MP Sormani, Francesca F Ficara, Simona S Di Terlizzi, Anna Maria AM Parodi, Ruhena R Sergeant, Miryam M Martinetti, Andrea A Bontadini, Francesca F Bonifazi, Daniela D Lisini, Benedetta B Mazzi, Silvano S Rossini, Paolo P Servida, Fabio F Ciceri, Chiara C Bonini, Edoardo E Lanino, Giuseppe G Bandini, Franco F Locatelli, Jane J Apperley, Andrea A Bacigalupo, Giovanni Battista GB Ferrara, Claudio C Bordignon, and Katharina K Fleischhauer

Blood 103(4):1417-24 (2004) PMID 14576061

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.

Referenced by 1 articles

DOI: 10.1182/blood-2003-04-1279
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