S. F. Goldmann

TAP2 gene polymorphism segregates with DR-DQ in DR/DP recombinant siblings.

RING 11, a second transport-associated gene (TAP2), has been recently identified in the DR-DP interval of the human class II region. Two predominant alleles, TAP2A and TAP2B, differing by 17 amino acids at the C-terminus of the ATP-binding domain are present in the Caucasoid population at frequencies of 79% and 21%, respectively. In the rat, polymorphism of the TAP genes were found to influence peptide loading of MHC class I molecules and, in humans, it was speculated that variation in peptide loading of HLA-B27 molecules might be also linked to factors altering antigen presentation presumably encoded in the HLA region. To determine whether TAP2 gene polymorphism may be relevant to peptide loading in humans, we typed 41 HLA-ABC, DR-identical pairs for TAP2A and TAP2B by PCR-SSO hybridization or direct genomic sequencing. In eight cases, GLO-different and, in six cases, DP-different recombinant siblings were included. Allele frequencies for TAP2A and TAP2B were as previously reported (74% and 26%, respectively). In all pairs, TAP2 gene polymorphism segregated with the DR-DQ type, mapping the TAP2 gene telomeric to the recombination hot spot in the DR-DP interval of the human class II region. We conclude that, in HLA-identical siblings, TAP2 gene differences are very unlikely to occur. Thus, in HLA-identical siblings, minor histocompatibility antigenic differences cannot be attributed to variant peptide loading due to TAP2 gene polymorphism.

Selection of unrelated bone marrow donors: does the current procedure warrant complete MHC class II identity?

Bone marrow transplantation from unrelated donors is being used increasingly for the treatment of patients with leukemia and several other hematologic disorders. Selection of unrelated bone marrow donors currently relies on serological HLA identity and negative mixed lymphocyte reactions between donor/recipient pairs. As serological HLA-DP typing is not feasible, we used the HLA-DPB1 oligonucleotide typing method to investigate whether the current selection procedure can guarantee complete MHC class II identity. In 40 consecutive patients, one third (62/193) serologically HLA-A, -B, -C, -DR and -DQ identical donors were found to be MLC-negative with a relative response below 5%. HLA-DPB1 oligonucleotide typing of these MLC-negative donors revealed that again only one third (20/62) was also identical for DP with their presumptive recipients. In the majority of pairs a disparity in graft-versus-host direction or in host-versus-graft direction of at least one allele was seen. These data indicate that, in spite of the strict MLC criteria used, the current procedure did not warrant complete MHC class II identity. This implies that oligotyping for DPB1 can improve matching and should be introduced for typing of volunteers.