DP Typing Research Articles

HLA-DP and HLA-DO genes in presumptive HLA-identical siblings: structural and functional identification of allelic variation.

We analyzed HLA class II genomic polymorphisms in three families in which bone marrow transplantation was performed between individuals presumed to be HLA identical, but in which unexplained mixed lymphocyte culture reactivity was observed. These families were characterized by classical HLA serology, MLC, and DP typing. In each family, a pair of "HLA-identical" siblings demonstrated a small proliferative response in bidirectional MLC. Southern blotting analysis performed with cDNA probes for DQ alpha, DP alpha, and DP beta identified DP genomic differences in each case. Hybridization of Bgl II-digested genomic DNA with a DP alpha cDNA probe revealed three prominent polymorphic fragments (7.7, 5.8, and 3.7 kb), which discriminated between presumptive identical siblings and indicated crossover events within HLA. Similarly, hybridization of SstI-digested genomic DNA with a DP beta cDNA probe, although resulting in a more complex pattern, identified DP genomic disparity between the presumed HLA identical siblings. Hybridization of SstI-digested DNA from two families with evidence of DP recombination was performed by using an oligonucleotide probe specific for the newly described HLA class II gene DO beta. Two major polymorphic fragments, at 6.2 and 3.3 kb, segregated in these families and localized the crossovers flanking the DO beta gene between the DQ and DP loci. The contribution of the antigenic differences marked by these HLA DP and DO DNA polymorphisms to allorecognition in MLR and in graft-vs-host disease are discussed.

Isolation and allelic polymorphism of cDNA clones and genomic clones of HLA-DP heavy and light chains

From a human cDNA library constructed from consanguineous HLA-homozygous cell line AKIBA (HLA-A24, Bw52, DR2, Dw12, Dp63 Cp63: a new DP type), cDNA clones encoding the heavy and light chains of an HLA-DP Cp63 alloantigen were isolated and analyzed by restriction enzyme mapping and nucleotide sequence determination. Allelic comparisons DPα and DPβ cDNA sequences showed that the amino acid sequence of the DPα chain was less polymorphic than that of the DPβ chain. In the polymorphic region was restricted to the β1 domain. We also isolated and characterized 15 genomic phage clones spanning a 74 kilobase (kb) pair of the DP region which were found to contain one DPα gene, one DP-like α gene, one DPβ gene, and one DP-like β gene. Genomic blot analyses with different HLA-DP type cell lines using DPα cDNA as a probe revealed EcoRI fragment length polymorphism around the DPα gene.

A polynomial-time algorithm for computing an optimal admission policy in a GI/ M/1/ N queue

A polynomial-time algorithm is proposed for computing an optimal admission policy for GI/ M/1/ N queueing systems. The approach is based upon mathematical programming in which a pointwise minimal value functions is to be found subject to a finite number of DP type constraints. The program is transformed by Fourier-Motzkin elimination into equivalent reduced systems to which a simple, forward-substitution type algorithm can be applied.

Recognition of DP determinants with typing reagents prepared with lymphocytes from Dutch unrelated individuals

In an attempt to make our own set of DP typing reagents, we used lymphocytes from 12 unrelated donors, who were all HLA-A1,2; B7,8; DR2,3; DQW1,2. They all had been previously typed for DP using a reference set of well established reagents obtained from Dr. S. Shaw (NIH, Bethesda). Thirty-six promising responder-stimulator combinations were primed in bulk MLC and tested for their specificity in secondary MLC. All reagents gave reaction patterns which were concordant with the sensitizing DP types, with the exception of those combinations where a donor was used in which DR2 appeared to be associated with a non-DW2 HLA-D type. Over 1,200 reactions obtained with the new reagents were compared with those obtained with the established ones, in six different experiments. High correlation coefficients (r values) were found between the two kinds of reagents. The typings of a panel of individuals with the reference set and with our new typing set revealed an excellent agreement for DP assignments with the two sets, with the exception of the specificity DP4. The DP gene frequencies for random Dutch Caucasoids were defined.

Typing for human alloantigens with the primed lymphocyte typing (PLT) technique with notes on the interpretation of PLT data

A typing system for HLA-D/DR-associated PLT-defined determinants, which have been called “DP” antigens, is reported. Some of the results concerning a data interpretation system, the reproducibility of PLT results, and the correlations between the results of HLA-D, -DR, and DP typing are presented. Also, a “new” human alloantigen, EP1, not belonging to the series of DP antigens, is defined with PLT.

HLA-A, B, C, D, DR antigens and primed lymphocyte typing (PLT) defined DP-antigens in juvenile chronic arthritis.

A total of 48 patients with juvenile chronic arthritis (JCA) were typed for HLA-A, -B, -C, -D and -DR antigens and 36 patients were also typed for HLA-D/DR associated "DR"-antigens with the primed lymphocyte typing technique. In the total group of patients, we found increased frequencies of HLA-B27, HLA-Dw/DP5 and HLA-Dw/DP8, and decreased frequencies of HLA-Dw/-DR/DP2. The increased frequencies of HLA-Dw/DP8 and the decreased frequencies of HLA-Dw/-DR/DP2 were primarily found among patients with persistent pauciarticular arthritis. The frequencies of HLA-Dw/-DR/DP4 were increased in patients with polyarticular arthritis. The frequencies of HLA-B27 and -Dw/DP5 were increased in both pauciarticular and polyarticular arthritis. The results indicate (i) that genetic factors controlled by HLA confer susceptibility and/or resistance to JCA, and (ii) that the clinical subdivision of JCA into pauciarticular and polyarticular JCA can be supported by the presence of different genetic markers (HLA-antigens) in the two groups of JCA-patients. If these data can be confirmed HLA-D, -DR or DP typing may be of value in the prognostic evaluation of patients with pauciarticular onset JCA.