Characterization of a new HLA-DPB1 allele, DPB1*010103.
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Alleles↗
Biomedical subjects
G F Fischer
Publications and source records attributed to G F Fischer.
Exon 1-4 sequence analysis of a novel HLA-A allele, HLA-A*2458.
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Alleles↗
A single amino acid exchange shifts the serological reactivity of the novel HLA-B*4442 allele product from HLA-B44 to HLA-B21.
A novel HLA-B (human leukocyte antigen-B) allele, HLA-B*4442, was identified both in a Czech patient with leukaemia and in his mother. The presence of a novel allele was initially suspected because conflicting results were obtained by serological and DNA typing techniques. The HLA typing using the polymerase chain reaction-sequence-specific primers (PCR-SSP) at the two-digit level indicated an allele belonging to the HLA-B*44 group, whereas serological typing indicated HLA-B21. Typing with PCR-sequence-specific oligonucleotides (PCR-SSO) resulted in a unique reaction pattern that could not be assigned to a known allele, PCR-SSP typing at the four-digit level did not match any known B*44 allele, either. The sequencing-based typing of the HLA-B locus then revealed the novel B*4442 allele that is identical with B*4405 except a single C-->G nucleotide exchange at position 572. This exchange results in an amino acid substitution from serine to tryptophan at position 167 of the expressed HLA-B protein. The B21 serological reactivity of the novel B*4442 allele product was confirmed by employing an additional serological panel of typing sera. Our findings support previous reports claiming that serine at the position 167 in the alpha-2 domain of the HLA-B protein is a major determinant of the HLA-B44(12) serological epitope.
Alleles↗
A novel HLA-B*2730 allele found in a Slovene patient affected with IgA nephropathy.
A novel allele HLA-B*2730 and the haplotype HLA-A*03-B*2730-Cw*02-DRB1*16-DRB5 have been found in a Slovene patient and his mother. The exon 2 sequence is identical to that of HLA-B*2702, and the exon 3 sequence is identical to that of HLA-B*2719. A possible mechanism for the generation of B*2730 is a gene conversion event.
Adult↗
Impact of HLA class I high-resolution mismatches on chronic graft-versus-host disease and survival of patients given hematopoietic stem cell grafts from unrelated donors.
There is consensus that matching of unrelated donors (URD) and patients for HLA class II alleles improves the outcome of hematopoietic stem cell transplantation (HSCT). However, the significance of HLA class I allelic mismatches for transplant outcome is under discussion and reports on long-term effects like chronic graft-versus-host disease (GVHD) are rare. Thus, we investigated the association of human leukocyte antigen (HLA) class I allele mismatches and outcome in 144 patients given HSCT from URD who were matched for HLA-DRB1, DRB3/4/5, and DQB1 alleles. The risk of chronic GVHD was significantly increased in patients with class I mismatched donors, the mismatch either detected by low- or high-resolution typing. A single HLA class I allele mismatch significantly increased the risk of chronic GVHD in multivariate analysis. Overall survival was significantly reduced in patient/donor pairs with more than one-allele class I mismatch. Thus, selection of unrelated donors for transplantation should be based on high-resolution HLA class I typing.
Adolescent↗
Characterization of the human T cell response to antigen 5 from Vespula vulgaris (Ves v 5).
BACKGROUND: The T cell reactivity to the major allergen of bee venom, phospholipase A2, has been thoroughly characterized. In contrast, only little is known about the human cellular response to major allergens from wasp venom. OBJECTIVE: To characterize the human T cell response to antigen 5 from Vespula vulgaris, Ves v 5. METHODS: Recombinant Ves v 5 was used to establish allergen-specific T cell lines (TCL) and T cell clones (TCC) from the peripheral blood of vespid-allergic and non-allergic individuals. Ves v 5-specific TCL were mapped for T cell epitopes using overlapping synthetic peptides representing the complete amino acid sequence of Ves v 5. Ves v 5-specific TCC were analysed for antigen-induced secretion of IL-4, IFN-gamma and IL-10. RESULTS: Seventeen distinct T cell epitopes were recognized by allergic individuals among which Ves v 5(181-192) was identified as a dominant T cell epitope. Partially different epitopes were observed in TCL from non-allergic subjects and the dominant epitope Ves v 5(181-192) was not prevalent in these cultures. Ves v 5-specific TCC isolated from allergic individuals did not show the typical T helper type 2 (Th2)-like cytokine profile in response to specific stimulation, i.e. high amounts of IL-4 and low IFN-gamma. TCC from non-allergic individuals showed a Th1-like cytokine pattern. CONCLUSIONS: Our findings provide evidence that the allergic T cell response to Ves v 5 is not Th2-dominated and that different immunogenic sites on this major wasp venom allergen are recognized by allergic and non-allergic individuals.
Allergens↗
A novel HLA-B*420502 allele identified by PCR-SSO/SSP routine typing and confirmed by Sequencing-based typing.
A novel human leukocyte antigen-B (HLA-B) allele, B*420502, was identified in a patient with leukemia (Caucasoid, Czech ancestry) and his mother during intrafamily search for the hematopoietic stem cell donor. The novel allele was initially detected by HLA typing at low resolution using both sequence specific primers and sequence specific oligonucleotides techniques that resulted in unique reaction patterns. The alleles of the HLA-B locus were separated by the haplotype-specific extraction technique. Sequencing of those alleles revealed a novel allele, B*420502, that is identical with B*420501 except a T-->G exchange (synonymous mutation) at position 618.
Alleles↗
Identification of a new HLA-C allele, Cw*0316, by sequence-based typing.
The presence of a new allele, Cw*0316, was detected in a Caucasian individual through an unusual association. Molecular typing of the individual by sequence-specific primers and sequence-specific oligonucleotides showed the presence of B*58, B*41 and Cw*17. Sequence-based typing revealed the additional presence of another human leucocyte antigen-C allele. The new allele showed four nucleotide differences with Cw*030202 at positions 559, 560, 589 and 594 in exon 3, leading to three codon changes, codons 187, 197 and 198. This resulted in two amino acid substitutions at positions 163 (L-T) and 173 (K-E) of the mature protein, which proved sufficient to abrogate serological reactivity with Cw3-specific sera.
Alleles↗
A novel HLA-DRB1*13 allele (DRB1*1357) identified by polymerase chain reaction with sequence-specific primers and direct sequencing.
We describe the identification of a new DRB1*13 allele, DRB1*1357*, found in two Austrian Caucasian individuals. The novel allele was initially suspected because analysis with sequence-specific primers resulted in an unusual pattern of amplification. Thereafter, exon 2 was further characterized by sequence-based typing. The nucleotide sequence of DRB1*1357 is identical to DRB1*1319 except for a single substitution in codon 47 (TAC to TTC) leading to a change from phenylalanine to tyrosine.
Alleles↗
HLA-B*8102*, a new allele found in an external proficiency testing scheme.
A new human leukocyte allele HLA-B*8102 has been identified in a cell provided by the UCLA International Cell Exchange scheme. The nucleotide sequences of exons 2 and 3 of the new allele are identical with HLA-B*8101. Four nucleotide differences, however, are observed in exon 1, three of them representing non-synonymous base changes.
Amino Acid Sequence↗
Molecular genetics of the HLA complex.
The Human Leukocyte Antigen (HLA) system can be defined as a set of glycoproteins which take up peptides intracellulary and become ligands for immune receptors once they are expressed on the cell membrane. Functional HLA molecules are trimers consisting of a heavy chain and a light chain which bind a peptide. The production of HLA molecules in the endoplasmic reticulum, their assembly and their trafficking to the cell membrane have been studied in great detail. A salient feature of HLA molecules is their polymorphism which is essentially a tremendous amount of variation in the amino acid sequence of mainly the heavy chain between different HLA types. Polymorphic chains of HLA molecules are encoded in the human major histocompatibility complex (MHC) on the short arm of chromosome 6. A map of the nucleotide sequence of the human MHC has been established. The polymorphism of HLA molecules, i.e. the HLA type, is intimately associated with the nature of the peptides bound. In principle, HLA molecules can bind a variety of different peptides. However, peptides with distinct biochemical features are preferentially bound according to the HLA-type. HLA-typing is applied clinically in transplantation and disease association. Recently, recombinant HLA molecules have been used as a tool to define the T cell receptor repertoire.
Alleles↗
An HLA class-II allele frequent in Eskimos and Amerindians is found in the Tyrolean Ice Man.
DNA was extracted from specimens derived from the calcaneus of the Tyrolean Ice Man under sterile conditions in a laboratory, where no DNA extractions and PCR experiments had been performed before. Agarose gel electrophoresis and ethidium bromide staining did not reveal any evidence of genomic DNA in the preparation obtained, indicating a high degree of DNA degradation. Nevertheless, we performed PCR amplifications with this sample using primer pairs specific for HLA class II alleles. HLA-DRB and DQB1 alleles were amplified in a nested PCR approach. In one of the reactions, we observed a distinct amplification product, which we directly sequenced. By comparing the obtained nucleotide sequence with a database of HLA alleles we assigned the HLA-DRB1*1402 type to the amplified sample. None of the investigators involved possesses this allele, indicating that no contamination with modern DNA had occurred. The HLA-DRB1*1402 allele is extremely rare in Europe, but is common in Inuits and South American Indians and has previously only once been identified in the laboratory.
Alleles↗
Serological and nucleotide sequence analysis of HLA-A*6812.
We describe a novel HLA-A allele, HLA-A*6812. HLA-typing of a patient was performed by serology and by DNA-based analyses. Cloning and sequencing of exons 2 and 3 revealed that the genotype consisted of a common HLA-A*0101 allele and the novel HLA-A*6812 allele. HLA*6812 is identical to HLA-A*68012 except for a single non-synonymous nucleotide substitution leading to an exchange of a threonine to an isoleucine residue at position 142 of the HLA-class I alpha chain. The allele was also found in the patient's mother. The novel HLA-A68 molecule is recognised by some but not all of our HLA-A28-specific sera. These results confirm that position 142 is important for the serological properties of the HLA-A molecule.
Alleles↗
Molecular genetics of HLA.
A review of the molecular genetics of the HLA gene complex from a tissue typer's point of view.
Alleles↗
Characterization of a novel HLA-A*24 allele containing an HLA-A*03 sequence motif.
HLA-A*2418 is described for the first time. It segregates in a Mendelian fashion. Serological analyses indicate that the new allele encodes epitopes from both HLA-A9 and -A3 specificities. Results from nucleotide sequencing analyses of polymerase chain reaction (PCR) amplification products derived from genomic and cDNA are compatible with those findings.
Alleles↗
Immune complexes from vasculitis patients bind to endothelial Fc receptors independent of the allelic polymorphism of FcgammaRIIa.
UNLABELLED: Cutaneous leukocytoclastic vasculitis is characterized by the deposition of circulating immune complexes, neutrophil extravasation, and vessel destruction, but mechanisms of circulating immune complexes capture within postcapillary venules are unknown. We demonstrate that circulating immune complexes from sera of vasculitis patients bind to cultured endothelium in an Fc gamma receptor IIa-dependent fashion. In lesional skin, endothelial cells bind immunoglobulin G2 > immunoglobulin G3 and immunoglobulin G4, but not immunoglobulin G1, even before obvious neutrophil transmigration and vessel damage. As the human Fc gamma receptor IIa proteins exist in two allotypes (one with a histidine at position 131, which binds immunoglobulin G1, 2, 3 and the other with an arginine at position 131, which binds immunoglobulin G1, and 3, but is unable to bind immunoglobulin G2), we expected an altered prevalence of histidine 131 forms in vasculitis patients. Sequence analysis, however, revealed an equal distribution of allotypes in patients and controls. In conclusion, circulating immune complex binding to endothelial Fc gamma receptor IIa is among the initial steps in the development of vasculitis. Although immunoglobulin G2 is the predominant subtype precipitated at endothelial surfaces, it is not required for fixing circulating immune complexes to endothelium, because patients homozygote for Fc gamma receptor IIa-arginine 131 equally develop leukocytoclastic vasculitis as those bearing the Fc gamma receptor IIa-histidine 131 allele. As immunoglobulin G1 is virtually absent in leukocytoclastic vasculitis lesions and immunoglobulin G4 does not bind to both Fc gamma receptor IIa alleles, these complexes, in addition to immunoglobulin G2, should contain immunoglobulin G3 in order to fix to vascular Fc gamma receptor IIa, at least in persons homozygous for Fc gamma receptor IIa-arginine 131. KEYWORDS: CD32/immunoglobulin G subtypes/leukocytoclastic vasculitis/microvessels.
Alleles↗
HLA-A*02172* adds to the heterogeneity of HLA-A*02 alleles.
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Alleles↗
MUC18/MCAM (CD146), an activation antigen of human T lymphocytes.
Extravasation and tissue infiltration of leukocytes and metastatic tumor cells require the regulated expression and function of adhesive and pro-proteolytic surface molecules. We demonstrate here that human T cells, upon activation, neo-express the melanoma metastasis-associated surface molecule MUC18/melanoma cell adhesion molecule (MCAM). Expression of MUC18/MCAM (CD146) on T cells could be identified with two mAbs (541-10B2 and 541-2E5) obtained after immunization with HUT102 T cells and found to react with activated T cells. The specificity of our mAbs for MUC18/MCAM (CD146) was revealed by 1) definition of the appropriate molecular mass of approximately 110 kDa unreduced and 120 kDa reduced, 2) reactivity of mAbs with MUC18/MCAM (CD146) cDNA-transfected mouse L cells, 3) conclusive crosswise immunoblotting experiments with MUC18/MCAM (CD146)-specific mAbs, and 4) N-terminal amino acid sequencing of precipitated protein. In vitro activation by PHA caused neo-expression of MUC18/MCAM (CD146) on peripheral blood T cells within 1 day of stimulation, reaching a maximum on day 3. In vivo expression of MUC18/MCAM (CD146) was confirmed on CD3+ T cells infiltrating delayed-type hypersensitivity lesions of the skin, on synovial fluid T cells of rheumatoid arthritis patients, and on distinct T leukemia cells. MUC18/MCAM (CD146) cell surface expression on activated T cells is mirrored by the presence of specific mRNA. Leukocytes of healthy donors do not show significant MUC18/MCAM (CD146) expression. The finding that MUC18/MCAM (CD146) is also expressed on activated T cells might suggest that this adhesion molecule is involved in the extravasation and/or homing of activated T cells.
Antibodies, Monoclonal↗