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Biomedical subjects

A Urlacher

Publications and source records attributed to A Urlacher.

At least 19 recordsLinked to original sources
PubMed1994

Homozygous human TAP peptide transporter mutation in HLA class I deficiency.

Human lymphocyte antigen (HLA) class I proteins of the major histocompatibility complex are largely dependent for expression on small peptides supplied to them by transporter associated with antigen processing (TAP) protein. An inherited human deficiency in the TAP transporter was identified in two siblings suffering from recurrent respiratory bacterial infections. The expression on the cell surface of class I proteins was very low, whereas that of CD1a was normal, and the cytotoxicity of natural killer cells was affected. In addition, CD8+ alpha beta T cells were present in low but significant numbers and were cytotoxic in the most severely affected sibling, who also showed an increase in CD4+CD8+ T cells and gamma delta T cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Susceptibility to relapsing polychondritis is associated with HLA-DR4.

OBJECTIVE: To determine the frequency of HLA class II antigens in Caucasian central European patients with relapsing polychondritis (RP). METHODS: HLA class I, DR, and DQ specificities were identified in 41 patients with RP, and the frequencies were compared with those in 204 healthy, unrelated control subjects. HLA typing was performed using the standard complement-dependent microcytotoxicity assay. HLA-DR genotyping of 12 DR4-positive RP patients and 57 controls was performed by allele-specific oligonucleotide probing after amplification of genomic DNA by polymerase chain reaction. RESULTS: A significant increase in DR4 antigen frequency was found in the patients (56.1%) as compared with that in healthy controls (25.5%) (Pcorr < 0.001). Genotyping of DR4-positive patients and controls revealed no predominance of any DR4 subtype. CONCLUSION: There are important clinical similarities and overlaps between RP and rheumatoid arthritis (RA). In RA, the association with DR4 has been well established. Our findings show that although there is a DR4 association with RP, the situation is sufficiently distinct from that of RA to imply considerable differences in pathogenesis of the two conditions.

Alleles↗
PubMed1993

Establishment and characterization of B-like lymphoblastoid cell lines by long-term culture of primary explants from human myasthenic thymus.

Using a simple method of long-term culture, it was possible to obtain B-like lymphoblastoid cell lines (LyCLs) from myasthenic thymuses. Successful cultures were carried out from 14 out of 15 hyperplastic thymuses and in 1 out of 3 myasthenic thymoma, whereas none of the 8 control thymuses, nor the 2 Myasthenia gravis-associated normally involuted thymuses, nor the Myasthenia gravis-associated lymphoma gave rise to LyCL. All the LyCLs secreted immunoglobulins (Ig), either IgG or IgM. None of these Ig reacted with acetylcholine receptor or with other antigens known to be often involved in autoimmune diseases. EBV antigens were found in all the LyCLs as well as in the corresponding donors at the time of thymectomy. HLA characterization of some LyCLs and the corresponding donors showed that class II MHC antigens were expressed normally or with mild differences. However, 86% of the LyCL tested did not express class I MHC antigens.

B-Lymphocytes↗
PubMed1992

DP epitope mapping by using T-cell clones.

To determine whether a correlation exists between the genomic HLA class II DP DNA polymorphism and cell surface expression and to detect the DP epitopes responsible for alloreactivity, anti-DP T-cell clones were generated against new PLT blank RFLP DPa and DPb-defined specificities. The clones were tested on the 10th IHWS B-LCLs and on local panel cells. Oligotyping of the tested cells made it possible to (a) correlate the DPa specificity with the DPB1*0402 specificity and (b) split DPb into DPB1*1001 and DPB1*1401. By comparing DNA sequences of the second exon to panel reactivity, the epitopes responsible for DPB1*1001 and 1401 were defined and attributed to beta-chain residues contributing to peptide selection inside the HLA groove. However, DNA sequences could not explain anti-DPa allospecificity, indicating that another structure not yet definable may be involved.

Amino Acid Sequence↗
PubMed1992

Complexity of the HLA-DP region: RFLP analysis versus PLT typing and oligotyping.

A total of 84 individuals were DP typed in parallel with the restriction fragment length polymorphism (RFLP) analysis and the primed lymphocyte test (PLT). Whereas 80% of the cases gave concordant results, the other 20% showed discrepancies for one of the two alleles carried by the typed individuals. Oligotyping, PCR-RFLP and sequencing confirmed the results found by PLT. The 20% discordant results obtained with RFLP led us to conclude that RFLP typing cannot replace PLT typing. From a more general point of view, the RFLP analysis revealed the DP region to be more complex than expected since for each given PLT DP defined specificity, more than one RFLP DP haplotype could be determined. These were possibly induced by crossing-overs or gene conversion events.

Alleles↗
PubMed1991

[HLA class II DP antigens and bone marrow transplantation].

The biochemical structure of the HLA class II DP antigens is close to that of the remainder DR and DQ isotypes. Nevertheless, they may play a peculiar functional role. Their importance in bone marrow transplantation, where a complete HLA class II identity between graft donor and recipient is requested, is not yet known. The detection of a DP mismatch by using the mixed lymphocyte reaction is quite difficult. The role of such a mismatch in the incidence of graft versus host disease (GVHD) or graft rejection has to be defined. Studies on large series of recombinant families, using oligotyping, are necessary.

Bone Marrow Transplantation↗
PubMed1991

IgM anti-idiotypes that block anti-HLA antibodies: naturally occurring or immune antibodies?

Using dithiothreitol (DTT) technique, IgM anti-HLA anti-idiotypic antibodies were detected in a multiparous multitransfused woman. These antibodies were able to inhibit the binding of specific IgG anti-HLA antibodies on their corresponding antigen. The recognized determinants were cross-reactive determinants since they were partially found on anti-HLA antibodies from unrelated individuals. By studying the patient's sera over a period of 2 years, no IgM-IgG switch was observed but the presence of these antibodies was stable in time, despite the disappearance of the idiotypes (anti-HLA antibodies). However, when looking at the patient's earlier serum, it was shown that these IgM anti-idiotypic antibodies were absent from the first available serum. Thus, these anti-idiotypic antibodies seem to behave both like natural and immune antibodies. The incidence of such antibodies in pretransplant patients is discussed.

Adult↗
PubMed1990

HLA-DR1 and DRw6 association in DR4-negative rheumatoid arthritis patients.

This study of 110 seropositive rheumatoid arthritis (RA) patients confirms the significant association of susceptibility to RA with HLA-DR4 specificity (P less than 0.001). The DR1 frequency is elevated in the entire seropositive patient group, reaching marginal significance (P less than 0.025). The DR4-negative patients, however, have a much higher prevalence of DR1 (P less than 0.001). Surprisingly, the DRw6 specificity is significantly increased in the remaining DR4- and DR1-negative patients (P less than 0.01). These results demonstrate that RA is not associated with a single HLA-specificity, but to various degrees with DR4, DR1, and DRw6. These findings, and particularly the newly recognized association with DRw6, support the hypothesis that functionally equivalent shared epitopes or conformations on otherwise distinct MHC molecules may confer risk for developing RA.

Arthritis, Rheumatoid↗
PubMed1990

A nucleotide substitution in a Bg1 II site is responsible for the RFLP discrimination between DPw4 and DPa.

In a previous work we showed that the two functionally different specificities DPw4 and DPa could only be differentiated by RFLP analysis using two mutually exclusive fragments (respectively, Bg1 II 5.29 kb for DPw4 and 7.24 kb for DPa). The DP Workshop synthetic analysis localized these fragments in the DPA2 pseudogene region. Our results demonstrate, however, that they are located between the A1 and B1 genes; the Bg1 II restriction site responsible for the 5.29 kb fragment was localized between the first and second exon of the DPB1 gene and inside the 7.24 kb fragment. A single mutation point inside this restriction site is responsible for the absence of the 5.29 kb fragment, changing the specificity attributed by RFLP typing.

Bacterial Proteins↗
PubMed1990

[Post mortem HLA phenotyping of donors of eyes. Evaluation of a serological method of microlymphotoxicity on lymphocytes and PHA lymphoblasts].

To increase the number of HLA typed corneas a microlymphocytotoxicity assay on lymphocytes and PHA lymphoblasts was investigated. A double immunofluorescence technique using magnetic beads coated with anti-T8 (for class I) and anti-DR (for class II) monomorphic antibodies was applied. Blood samples from 50 non selected donors were obtained. HLA class I and class II typing was possible in 74% of the cases. Using PBL's (Peripheral Blood Lymphocytes) HLA class I could be defined in 29 out of 50 Cases and class II in 15 out of 50 cases. On PHA blasts HLA class I and class II antigens could be defined in 32 and 33 out of 50 cases respectively. Mean time of culture was 10 days (6-20). No influence of donor age and post partum time could be observed. By combination of both methods a significant proportion of eye donors could be reliably typed within a short time.

Adult↗
PubMed1989

A T-cell clone recognizing an MLC stimulating epitope located on the DRw11 beta 1 chain.

An alloreactive proliferative T-cell clone, 6065 WS, was obtained in an intrafamilial cell combination where the stimulator was a homozygous DRw11, DRw52, DQw3 son and the responder his haploidentical mother. Proliferation assays on eight local DRw11 families, 75 homozygous B-cell lines (Tenth Histocompatibility Workshop panel) and blocking assays with monoclonal antibodies showed that clone 6065 WS recognizes an epitope on the DRw11 beta 1 chain. Comparison of the reactivity of clone 6065 WS with cells expressing the three known DRw11 beta 1 amino acid sequences identified two unique amino acids at positions 71 and 86 which contribute to determining the specific recognition by the T-cell clone 6065 WS. Our data suggest that one or both of these amino acids can either be directly involved in the recognition by the T-cell receptor or responsible for critical conformation of the determinants on the DR molecule. Alternatively, they could affect recognition of a self peptide bound to the major histocompatibility complex class II molecule.

Amino Acid Sequence↗
PubMed1989

Routine HLA-DP typing by RFLP analysis.

HLA-DP typing using the Primed Lymphocyte Test (PLT) is a long and cumbersome technique requiring DP sensitized clones and bulk reagents. We describe here the use of restriction fragment length polymorphism (RFLP) analysis. This method is quicker and was found to be reliable after comparative analysis of the results between PLT and RFLP in 15 local families and 72 core cell lines from the Tenth International Histocompatibility Workshop.

DNA Probes↗
PubMed1989

Class II alloantigen expression on leukemic cells.

Class II antigen expression on leukemic cells has been mainly studied using monoclonal antibodies (Mabs). On the other hand, class II polymorphism has been mainly studied using alloantisera. The present study shows that the reactivity of leukemic cells from different lineages with class II Mabs was not always the same as that obtained with alloantisera and that the reactivity varied depending on the leukemic cell-type studied.

Antibodies, Monoclonal↗
PubMed1988

Autoreactive T cells in rheumatic disease. II. Function and specificity of an autoreactive T helper cell clone established from a HLA-B27+ reactive arthritis.

T cell lines were established by limiting dilution of peripheral blood (PBL) and synovial fluid lymphocytes (SFL) of a patient with HLA-B27+ reactive arthritis. Among these cell lines, the CD4 phenotype was dominant. Functionally, the majority of these cell lines exhibited helper activity for the immunoglobulin production by autologous B cells and proliferated in response to autologous mononuclear cells. In most cases, this autoreactive response was associated with alloreactivity. Only one cell line, the autoreactive CD4+ T cell clone, UA-S2, which was derived from the synovial fluid, proliferated in a highly specific manner in response to a determinant associated with MHC class II products present on autologous mononuclear cells. The restriction element was shown to be associated with DR molecules by inhibition experiments with monoclonal antibodies. Within the patient's family, the capacity of mononuclear cells to stimulate a proliferative response of UA-S2 segregated together with the HLA haplotype A2 or 32, B27, Cw1, DRw11 which was contributed by the patient's mother. UA-S2 proved to be a functional helper T cell clone. In the absence of additional antigen or mitogen, it induced IgG and IgM synthesis of autologous and family members' B cells. This helper activity of UA-S2 showed the same MHC restriction as the proliferative response. Although the patient's father also typed DRw11, this haplotype was not recognized by UA-S2. It is suggested that this autoreactive T cell clone detects a microheterogeneity of the serologically defined DRw11 haplotype. Indeed, typing of the patient's family members with cellular reagents established a difference between the two DRw11 haplotypes.

Arthritis, Rheumatoid↗