Significantly higher frequencies of alloreactive CD4+ T cells responding to nonpermissive than to permissive HLA-DPB1 T-cell epitope disparities.

摘要

Increasing evidence suggests that donor-recipient disparities for human leukocyte antigen (HLA)-DPB 1 can be of clinical importance in unrelated hematopoietic stem cell transplantation (HSCT). Two overlapping algorithms for functional T-cell epitope (TCE) matching involving 3 (TCE3) or 4 (TCE4) groups of DPB1 alleles have previously been shown to be significantly predictive of survival after 10/10 and 9/10 matched unrelated HSCT. In both TCE3 and TCE4, nonpermissive mismatches are directed against 2 groups of immunogenic antigens encoded by DPBl~*09:01, 10:01, 17:01 (TCE3/4 group 1) and DPBl~*03:01, 14:01, 45:01 (TCE3/4 group 2), respectively.2 In TCE3, all other frequent DPB1 alleles including DPBl~*02:01, 04:01, 04:02 and others are classified as poorly immunogenic TCE3 group 3, and DPB1 mismatches against these alleles are predicted to be permissive. In TCE4, TCE3 group 3 is further subdivided into 2 separate groups comprising DPB1~*02 (TCE4 group 3) and the other alleles (TCE4 group 4), with intermediate and poor immunogenicity, respectively.