HLA-B35-SUBTYPE MISMATCHES IN ABDR SEROLOGICALLY MATCHED UNRELATED DONOR-RECIPIENT PAIRS

We have characterized HLA incompatibilities in a group of 17 B35-posit ive patients who were ABDR matched (AB serology and oligotyping for DR 1-14) with their 28 (unrelated) potential bone marrow donors. High-res olution oligotyping for DR subtypes disclosed that nine combinations w ere in fact DR mismatched. Cytotoxic T-lymphocyte (CTL) activity was d etected in nine combinations (32%). In the group matched for DR subtyp es, three (16%) of 13 combinations were CTL positive. Patient-specific cytotoxic activity appeared to be directed against HLA C (two cases) or against a subtype of B35. In the group of DR-subtype-mismatched com binations, CTL activity was found in six (67%) of nine pairs. In all f our cases chat were studied in detail, however, CTL reactivity appeare d to be directed against a variant subtype of B35. We have studied the B35 incompatibilities recognized in five different combinations by sp ecificity analysis of the B35-specific CTLs and by partially sequencin g of relevant segments of B35 exon 3. Preliminary data show that, with in this relatively small Caucasoid group, at least five B35-variant su btypes could be distinguished. This would make B35 an antigen that wil l be frequently subtype mismatched, in particular when DR matching is done with low resolution (DR1-14) only.