HLA-B35-subtype mismatches in ABDR serologically matched unrelated donor-recipient pairs.
We have characterized HLA incompatibilities in a group of 17 B35-positive patients who were ABDR matched (AB serology and oligotyping for DR1-14) with their 28 (unrelated) potential bone marrow donors. High-resolution oligotyping for DR subtypes disclosed that nine combinations were in fact DR mismatched. Cytotoxic T-lymphocyte (CTL) activity was detected in nine combinations (32%). In the group matched for DR subtypes, three (16%) of 19 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 combinations, CTL activity was found in six (67%) of nine pairs. In all four cases that were studied in detail, however, CTL reactivity appeared to be directed against a variant subtype of B35. We have studied the B35 incompatibilities recognized in five different combinations by specificity analysis of the B35-specific CTLs and by partially sequencing of relevant segments of B35 exon 3. Preliminary data show that, within this relatively small Caucasoid group, at least five B35-variant subtypes could be distinguished. This would make B35 an antigen that will be frequently subtype mismatched, in particular when DR matching is done with low resolution (DR1-14) only.
Department of Medicine, Canton Hospital, University of Geneva, Switzerland.
N
N
Rufer
B
B
Breur-Vriesendorp
J M
JM
Tiercy
D
D
Gauchat-Feiss
X
X
Shi
A
A
Slavcev
N
N
Lardy
B
B
Chapuis
A
A
Gratwohl
D
D
Speiser
D015234:HLA-A Antigens / Q000276:immunology*; D015235:HLA-B Antigens / Q000276:immunology*; D015797:HLA-B35 Antigen / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology*; D006648:Histocompatibility / Q000276:immunology*; D006801:Humans; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015797:HLA-B35 Antigen; D006684:HLA-DR Antigens