1,720,979 research outputs found
HLA-DPB1 mismatch at position 69 is associated with high helper T lymphocyte precursor frequencies in unrelated bone marrow transplant pairs
No full textHLA incompatibility between bone marrow recipient and unrelated donor pairs is often associated with severe acute graft-versus-host disease following bone marrow transplantation. Due to the extensive polymorphism of HLA genes, finding genotypically identical pairs is a difficult challenge. Therefore, it is crucial to single out the relevance of each HLA gene and, within each sequence, the polymorphic positions that induce a T-cell response. Among HLA class II genes, the relevance of HLA-DPB1 in inducing graft-versus-host disease is still controversial. In this study, we selected 37 bone marrow transplant pairs on the basis of HLA class I A and B identity as determined by isoelectric focusing and of class II identity as determined by serology and by low-resolution genomic typing. We analyzed them for the possible relationship between frequency of cytotoxic T lymphocyte and helper T lymphocyte precursors (CTLp and HTLp, respectively) and genomically determined class II mismatches. Seventeen pairs had high numbers of both CTLp and HTLp. They were not further considered because of the difficulty in determining whether the T-cell response was induced by class I or class II mismatches. Of the remaining pairs with low CTLp and high HTLp, six had disparities at HLA-DRB1 and HLA-DPB1 genes, and 14 differed only at the HLA-DPB1 locus. Among the latter pairs, we found a correlation between HLA-DPB1 mismatches and HTLp frequency, thus suggesting that disparity at this locus influences the alloreactive T-cell response. When the HTLp frequency was correlated with each single mismatch found in the 14 pairs, it appeared that the nature of the amino acid at position beta69 played a relevant role in inducing alloreactivity
The HLA-DP locus in bone marrow transplantation
No full textThe outcome of bone marrow transplantation has been shown to be improved by matching of the HLA class I and class II antigens. As to the HLA class II, while there is a general agreement on the relevance of HLA-DR matching, the role of other HLA class II loci remains to be established. Among these, there is a growing interest for the possible role played by the HLA-DP locus because of its extensive polymorphism. Analysis of the correlation between DP compatibility and graft survival has been so far hindered by technical difficulties. In fact, DP allelic products cannot be easily typed serologically and, at the genomic level, the standard SSO technique foresees the use of 20 labelled oligoprobes. We have recently described a simple electrophoretic technique that, applied to HLA-DPB1 locus, is at least as discriminative as oligotyping, but it does not require probes. This method is based on the changes of the suprahelical structure of HLA molecules produced by mismatched base pairs in critical positions. These conformational changes in turn produce a degree of retardation in electrophoresis which can be allele-specific. We think that this technique, which has proven to be useful in the typing of several HLA loci, is particularly suitable for this kind of study where, often, a small number of samples at a time needs to be analyzed
MICA exon 5 microsatellite typing by DNA heteroduplex analysis: a new polymorphism in the transmembrane region
No full textMICA (MHC class I chain-related gene A) is localized 47 kb upstream from HLA-B on the short arm of chromosome 6. It has been postulated that MICA protein folds similarly to the class I chain and may have the capacity to bind short ligands. Short tandem repeats (STR) within the transmembrane (TM) region of this gene have been described and five alleles consisting of 4 to 9 GCT codons, each encoding an alanine residue have been defined. We have applied DNA heteroduplex analysis to type MICA trinucleotide repeats in order to develop a simple and reliable method for their identification. This approach allowed the characterization of all MICA alleles. Moreover, a new polymorphism within the TM region was identified
A new approach to HLA-DPB1 typing combining DNA heteroduplex analysis with allelic specific amplification and enzyme restriction
No full textAllelic polymorphism of HLA-class II antigens plays a key role in the regulation of the immune response and in transplantation immunity. The allelic diversity of these antigens can now be analyzed at the DNA level after amplification by polymerase chain reaction. In this study we apply a simple technique based on the electrophoretic analysis of DNA heteroduplexes to the typing of HLA-DPB1 alleles. In order to increase its resolution, a group-specific amplification was used which subdivides the 19 HLA-DPB1 alleles in two non-overlapping families. A separate analysis was then performed within each group of alleles. This approach allowed an unequivocal one-step typing of the alleles belonging to group 1 which comprises few alleles of high frequency. Some group 2 alleles require, as a further step, the test with a restriction enzyme. The combination of more than one technique represents, in our opinion, the easiest way to solve the micropolymorphism of class II alleles. We conclude that this method, which is very simple, quick, and accurate and does not require probes, may become the method of choice for HLA-DPB1 typing
Divergent action of cobalt salts on the fate of peripheral blood monocytes and T lymphocytes
No full textSusceptibility to hard metal lung disease is strongly associated with the presence of Glutamate 69 in HLA-DP beta chain
No full textClinical, epidemiological and experimental data indicate that inhaled metal dust containing cobalt may produce an interstitial lung disease termed "hard metal disease" (HMD). Some aspects of this pathology such as the lack of correlation with dose exposure, the low frequency of the disease and the presence of T cells in the inflammation site, all suggest the existence of a genetic susceptibility, possibly to an immunological response to cobalt or to self proteins modified by cobalt. Here we report that HMD is strongly associated with residue Glu-69 of the HLA-DP beta chain. All patients, except for one with a rare genotype, possessed this marker as compared to 17 out of 35 exposed unaffected individuals (p = 0.0014). These data allow us to genetically distinguish a subgroup of cobalt-exposed individuals at risk for HMD, independently from the more common allergic reaction
Spondilite Anchilosante ed un nuovo allele HLA-B27 non associato alla malattia. Implicazioni patogenetiche
No full textMICA exon 5 microsatellite typing by DNA heteroduplex analysis: a new polymporphism in the transmembrane region
No full textMICA (MHC class I chain-related gene A) is localized 47 kb upstream from HLA-B on the short arm of chromosome 6. It has been postulated that MICA protein folds similarly to the class I chain and may have the capacity to bind short ligands. Short tandem repeats (STR) within the transmembrane (TM) region of this gene have been described and five alleles consisting of 4 to 9 GCT codons, each encoding an alanine residue have been defined. We have applied DNA heteroduplex analysis to type MICA trinucleotide repeats in order to develop a simple and reliable method for their identification. This approach allowed the characterization of all MICA alleles. Moreover, a new polymorphism within the TM region was identified
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