ACUTE GRAFT-VERSUS-HOST DISEASE AFTER BONE-MARROW TRANSPLANTATION WITH A SINGLE HLA-DPB1-ASTERISK-1001 MISMATCH - INVOLVEMENT OF DIFFERENT TCRBV SUBSETS

HLA-DP incompatibility is not considered as an exclusion criterion for bone marrow donors, because such incompatibility was not shown to aff ect significantly the risk for acute graft-versus-host disease (GVHD). In line with this clinical observation, it was proposed that in the c ontext of bone marrow transplantation, HLA-DP determinants did not fun ction as transplantation antigens in the same way as HLA-A, -B or -DR, In contrast to the above conclusion, we recently demonstrated the pre sence of HLA-DPB10501 specific T cell clones in a skin biopsy of a pa tient who developed aGVHD after receiving a bone marrow transplant (BM T) in which the only mismatched allele in the GVHD direction was HLA-D PB10501, At that time, this case was unique and occurred in a relativ ely uncommon graft setting where the patient received purified CD34(+) BM cells from an unrelated donor. In the present study, we analyzed t he immunological events associated with an aGVHD which occurred in the context of a 'regular' allogeneic BMT involving a single HLA-DPB1100 1 mismatch between donor and recipient in the GVHD direction. To this end, we analyzed several amplified T cell subsets present within a T c ell line derived from a skin biopsy performed at the onset of GVHD, Ou r results demonstrated that T cell populations belonging to the TCRBV2 , TCRB6.7, TCRBV14 and TCRBV17 subsets were specific for the HLA-DPB1 1001 mismatched allele, These data strengthen and generalize our first conclusion that a single HLA-DP mismatch between donor and recipient can activate a strong T cell response in vivo and consequently challen ge the notion that HLA-DP incompatibility should not be taken into acc ount in the choice of BM donors. Moreover, they also underline the ide a that HLA-DP antigens may represent an interesting immune target for future therapeutic approaches.