T h e h u m a n major histocompatibility region, HLA-D, controls the expression of a n u m b e r of polymorphic antigens exhibiting limited tissue distribution. Two sets of antigens, SB and DR, controlled by separate loci within the H L A -D region (1-3), exhibit similar functions relating to antigen presentation and T cell regulation (4-7). Recent studies have d e m o n s t r a t e d that a mo;~oclonal antibody, I-LR1, is reactive with some of the allelic products of the SB locus (8). Using the I-LR1 a n t i b o d y to isolate SB antigens, it has been shown that the two chains resemble the a l p h a and beta chains of the D R antigens in molecular weight as measured by sodium dodecyl sulfate (SDS) gel electrophoresis (9). These and other parallels between SB and D R antigens suggest a structural relationship between the two sets of antigens. This study describing a portion of the amino-terminal a m i n o acid sequences of these molecules delineates that relationship and suggests that the a l p h a and beta chains of the SB antigens are structurally distinct from the D R a l p h a and beta chains and that SB antigens, like D R antigens, are homologues of the murine I-E antigens.
Since the advent of the European Marrow Donor Information System in the first half of the last decade, fully automated data exchange between registry computer systems has been playing an ever-increasing role in the international search for unrelated donors of blood progenitor cells. This exchange, however, was hampered by different local conventions used to present HLA data and complicated by the need to extend the official WHO nomenclature to accommodate the registries' information systems and to cross-validate HLA data obtained with different methods and/or at different loci. The guidelines presented here have been developed by the World Marrow Donor Association to standardize the nomenclature to be used and the validation checks to be applied in the international electronic exchange of HLA-typing data among unrelated volunteer hematopoietic stem cell donor registries and umbilical cord blood banks. Two reference web sites have been designated to maintain and update the approved HLA nomenclature and all the ancillary information needed by the conventions described here.
Monoclonal antibody IVD12 was used to isolate and characterize a human Ia molecule present on B cells that generally display DR4 or DR5 phenotypes. The specificity of binding of IVD12 to human peripheral blood B cells from 75 normal individuals and 19 homozygous human lymphoblastoid B cell lines was identical to the supertypic specificity MB3 previously defined. Furthermore, IVD12-reactivity was shown to segregate with HLA in three informative families. In each family, individuals positive for IVD12 binding were also positive for DR4 or DR5. Using IVD12, a molecule has been isolated from the homozygous cell line PRIESS (DR4/4) and has been shown by amino acid sequence analysis to be homologous to the murine I-A and human HLA-DS molecules. These findings suggest that the MB3 specificity is found on a molecule encoded by loci distinct from those loci which encode HLA-DR molecules. This molecule represents the third family of HLA-D region molecules isolated from the cell line PRIESS. Both HLA-DR and HLA-SB molecules from this cell line were previously shown by amino acid sequence analysis to be I-E-like but distinct from one another. Collectively, these data provide evidence that the HLA-D region contains at least six loci encoding distinct alpha and beta chains for the HLA-SB, HLA-DR, and HLA-DS molecules.
The antigens encoded in the HLA-D region of the human major histocompatibility complex (MHC) 1 were originally defined with homozygous typing cells by mixed leukocyte culture and, subsequently, by use of human alloantisera reacting with antigens selectively expressed on B cells (1, 2). These antigens were later shown to be the human equivalents of the murine Ia molecules. The major serologically defined specificities, called DR, were found to be closely associated with the specificities defined by HTCs. Later, the development of ailoantisera permitted identification of additional serologic specificities such as DC, MB, MT, and Te (3-8) which are not associated with a single DR specificity but, instead, are found associated with two or more DR alleles and are, therefore, called supertypic. For example, MT2 is usually found on DR3-, DR5-, DRw6-, or DRw8-bearing cells while MT3 is usually found on cells from DR4-, DR7-, or DRwg-positive donors. The apparent equivalence of terms used by different investigators is shown in Table I (see also reference 3).Studies of the structural bases for these serological specificities have focused on three types of molecules that have been described biochemically. In a total Ia isolate, DR molecules are the predominant set of HLA-D region antigens and are homologues of the murine I-E molecules (9). These molecules bear the DR serologic specificities, which have been shown to be associated with their polymorphic beta chains (9). A DR homozygous cell line expresses DR molecules that are a set of closely related proteins which appear to share a single alpha chain and possess several structurally distinct beta chains (10, 1 1). It is not clear if all of these 1-E-like species carry the DR serologic determinants that are defined with alloantisera. The DS (DC) antigens are homologues of the murine I-A antigens (12) and bear the MB serologic determinants (13,14).
Summary:Filgrastim (r-metHuG-CSF)-mobilized peripheral blood progenitor cells (PBPC) and unstimulated bone marrow (BM) were evaluated and compared for reconstitution after high-dose chemotherapy in patients with relapsed Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) with respect to engraftment, overall and relapsefree survival, and contamination by lymphoma cells using molecular analysis of immunoglobulin gene rearrangements. Forty-four patients with either NHL or HD underwent autologous transplantation after highdose chemotherapy. Patients were randomized to receive either Filgrastim-mobilized PBPC (n = 15) or unstimulated BM (n = 14). An additional 15 patients received PBPC without randomization because of a recent history of marrow involvement by lymphoma. Use of PBPC was associated with faster neutrophil engraftment than BM (11 vs 14 days to an absolute neutrophil count Ͼ0.5 × 10 9 /l, P = 0.04), but without any difference in platelet engraftment, infectious complications, or overall or event-free survival. Both BM (65%) and PBPC (73%) were frequently contaminated by tumor cells as assessed by CDR3 analysis. Patients with negative polymerase chain reaction analysis of a BM sample during the study had a trend towards an improved survival; however, BM involvement by disease had no impact on the ability to mobilize or collect PBPC. We conclude that PBPC are as effective as BM in reconstituting hematopoiesis after high-dose chemotherapy and that both products are frequently contaminated by sequences marking the malignant clone.
Summary:This special report details the World Marrow Donor Association's recommended procedures regarding the international search for an unrelated donor for hematopoietic stem cell transplantation. The responsibilities of the national hubs, transplant center and donor registry staff are outlined for all actions associated with the preliminary search, formal search, donor confirmatory typing and final donor selection.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.