PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “HLA polymorphism”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 307 records · Page 17Linked to original sources
PubMed1989

Two cytotoxic human-human hybridoma antibodies to HLA: TrAH10 (anti A3.1) and TrAG2 (anti B7, Bw42).

Two cytotoxic human-human hybridoma IgM antibodies to HLA were generated by EBV transformation of PBMC from multiparous women and fusion of EBV transformed cells with the human fusion partners KR4 or KR12. Both mAbs required the sensitive immunomagnetic cytotoxicity method to display killing of freshly prepared PBMC. One mAb (TrAH10) was specific for HLA-A3. Strikingly, TrAH10 reacted much more strongly with lymphoblastoid cell lines of HLA-A3.1 than of the rare variant HLA-A3.2, previously detected by cytotoxic T cells. Thus, in the microcytotoxicity test, the titer of concentrated TrAH10 was approximately 2000 times higher for A3.1 as compared to A3.2, and a clear difference was also observed in radioimmunoassay. Since the two HLA-A3 variants differ by only two amino acids at positions 152 and 156 of the alpha 2-domain's alpha-helix, the epitopes defined by the mAb TrAH10 and HLA-A3.1 specific cytotoxic T cells must be closely related. The observations with TrAH10 suggest that the HLA polymorphism detected by human mAbs may turn out to be as extensive as the T-cell defined HLA polymorphism. The other mAb (TrAG2) bound B7 and Bw42 with equal strength, and in addition bound weakly to some cells that were Bw22 or B39. Magnetic polymerbeads coated with affinity purified human mAbs TrAH10 or TrAG2 formed rosettes with EBV transformed cells carrying relevant HLA antigens; however, rosette formation with freshly isolated PBMC was very weak and unsuitable as a typing assay.

Antibodies, Monoclonal↗
PubMed2006

Association of TNF-alpha genetic polymorphism with HLA DPB1*0301.

BACKGROUND: We speculated TNF-alpha can be one of candidate gene for aspirin-intolerant asthma (AIA) because TNF-alpha is pro-inflammatory cytokine and known to be increased level in asthmatic airways. In addition, genetic interaction between TNF-alpha and human antigen leucocyte (HLA) DPB1*0301, which is a strong genetic marker for AIA, was examined for its close location within chromosome 6. METHOD: To investigate genetic association of TNF-alpha with an AIA phenotype, three study groups (163 patients with AIA, 197 patients with aspirin-tolerant asthma (ATA), 257 normal control subjects) were enrolled. Single nucleotide polymorphisms (SNPs) were genotyped using a single-base extension method and HLA DPB1 genotyping was determined by high-throughput sequencing method. RESULTS: All five SNPs of TNF-alpha were tested; there were no significant differences in allele and genotype frequencies among the three groups. However, significant association between TNF-alpha-308G>A polymorphism and atopy status was noted (P<0.05). Gene to gene interaction between TNF-alpha-1031T>C (or -863C>A or -857C>A) and HLA DPB1*0301could synergistically increase the susceptibility to AIA with odds ratio (OR) to 7.738 (or OR=8.184 for -863C>A, OR=7.500 for -857C>T, P<0.001, respectively). CONCLUSION: TNF-alpha promoter polymorphism may significantly increase susceptibility to AIA by gene-to-gene interaction with HLA DPB1*0301.

Adult↗
PubMed1992

Automated measurement of cell destruction: the Patimed system in comparison with conventional HLA typing and the cell mediated lympholysis test (CML).

The key role of HLA polymorphism in the pathogenesis of many diseases and in determining compatibility in transplantation makes it desirable to employ automated systems for identifying HLA polymorphism. For more than one year we have used the photometer system Patimed commercially available from the Leica company. We compared the results of the conventional cell-mediated lympholysis test and conventional serological HLA typing with the results obtained by the Patimed system. Despite some good preliminary results it would be premature, in our opinion, to recommend the Patimed system for routine assessment of killer cell activity whereas we can definitely recommend the Patimed system to define HLA class I and class II molecules serologically for research or routine purposes.

HLA Antigens↗
PubMed2001

Ramifications of HLA class I polymorphism and population genetics for vaccine development.

HLA polymorphism can complicate the design and development of vaccines, especially those that contain a selected number of epitopes and are directed at pathogens prevalent worldwide. Because of HLA class I restricted antigen recognition and ethnic variation in HLA distribution, such vaccines may not be uniformly effective across populations. We, therefore, considered whether it is possible to assemble a panel of HLA-A and/or HLA-B alleles that would allow the formulation of a single vaccine for a set of Caucasian, Black, or Asian populations. In applying an algorithm to predict levels of favorable response, we identified predominant alleles in 15 representative populations. Approximately 80% of the individuals in one African Black population and five Asian populations were positive for at least one of three HLA-A alleles. Eighty percent coverage was also theoretically possible in five Caucasian populations with only five HLA-A alleles. Four of five Black populations analyzed also required five alleles, but the allelic combinations differed. Our findings suggest that HLA-A alleles may be preferred targets because of the increased heterogeneity at HLA-B, although addition of a single HLA-B allele to a set of HLA-A alleles improved coverage. This approach provides for the identification of combinations of alleles that represent a desired percentage of a population and that could be targeted in designing vaccines. For vaccines with known HLA-restricted epitopes, it allows a prediction of theoretical levels of "responder" and "non-responder" status. Finally, these results might be used in the analysis of protein sequences to identify potential CD8+ T-cell epitopes in populations of interest. Biologic variables that may have further relevance are discussed.

Algorithms↗
PubMed2003

Genetic polymorphism of HLA DR in a Scottish population of patients with pars planitis.

PURPOSE: Human leucocyte antigen (HLA) class II influences the immunological susceptibility for a variety of diseases including many types of non-infectious intraocular inflammation. Previous studies on North American patients with pars planitis, a subtype of intermediate uveitis, reported an increased prevalence of HLA DR15 in this population. In contrast, two European studies could not find an association between HLA DR2 or its allelic subtype DR15 and various forms of intermediate uveitis. We therefore investigated the genotype frequency of HLA DR alleles in a Scottish population of patients with typical pars planitis. METHODS: Twenty patients with pars planitis were identified from the uveitis database of Grampian University Hospitals. Only patients with bilateral vitritis and snowbanks in at least one eye in the absence of systemic disease were included in the study. Fifteen patients and 34 healthy controls underwent HLA DR genotyping for all DRB genes using PCR sequence specific primers. RESULTS: HLA DR15 was found in 13% of patients with pars planitis and in 24% of controls. There was no statistically significant difference between these two groups. Furthermore, the frequencies of HLA DR 1, 3-14, and 16 did not differ significantly between patients and controls. CONCLUSIONS: There appears to be no association between the occurrence of pars planitis and the HLA DR15 or other known HLA DR genotypes in Scottish patients. However, the small sample size limits the power of this study.

Alleles↗
PubMed1991

[Polymorphisms of HLA class II antigens in 33 Japanese pemphigus patients].

The HLA class II antigens in 33 Japanese pemphigus patients were investigated by both serologic and restriction fragment length polymorphism (RFLP) analyses: 17 cases of pemphigus vulgaris (PV), 13 cases of pemphigus foliaceus (PF), 3 cases of unclassified pemphigus. In serologic typing, DR2 was absent in PV. DR5, DRw6, DRw12, and DRw52 were positively associated with PV. DQw1 was positively associated with PF. RFLP analyses showed that DRw6 PV patients had a disease-associated restriction fragment representing DQw5, the same association as that found in DRw6 Jewish PV patients. On the other hand, all 13 PF patients were serologically typed for DQw1, which could not be further subdivided into DQw5 by RFLP analyses. These results suggest that Japanese and Jewish PV patients may be immunogenetically closely related to each other, but Japanese PV patients appear to be immunogenetically different from Japanese PF patients.

Asian People↗
PubMed1995

HLA DPB polymorphism in primary sclerosing cholangitis and primary biliary cirrhosis.

In recent years there has been an increasing interest in the link between susceptibility to autoimmune liver disease and genes of the HLA system, although the role of the DPB1 locus in British patients has only been investigated in autoimmune hepatitis. The aim of the current study was to determine the distribution of DPB1 alleles in a large series of British patients with the two other autoimmune liver diseases, primary biliary cirrhosis and primary sclerosing cholangitis, and compare the allele frequencies obtained with those of a geographically matched control group. Polymerase chain reaction sequence-specific oligonucleotide probing was used to assign 18 DPB1 alleles in 82 patients with primary biliary cirrhosis (PBC), 71 patients with primary sclerosing cholangitis (PSC), and 103 controls. The frequencies of the DPB1 alleles were not significantly different comparing patients and controls. However, two important observations were made. Firstly, in primary sclerosing cholangitis, the previously reported association with the haplotype A1-B8-DR3-DQ2 does not extend to the DPB1 locus, suggesting that the genetic determinants of susceptibility for this disease lie closer to the DRB loci. Secondly, in primary biliary cirrhosis there is evidence that the reported association with DR8-DQB1*0402 includes the DPB1*0301 allele. The weak HLA association reported here is in contrast with recent data from Japan, where susceptibility is strongly linked to a particular amino acid residue encoded by the DPB1*0501 allele. These data clearly demonstrate that the alleles of the DPB1 locus are not associated with susceptibility to or protection from either primary biliary cirrhosis or primary sclerosing cholangitis in British patients.

Adult↗
PubMed2000

HLA-B polymorphism affects interactions with multiple endoplasmic reticulum proteins.

To explore the nature of amino acid substitutions that influence association with TAP, we compared a site-directed mutant of HLA-B*0702 (Y116D) to unmutated HLA-B7 in regard to TAP interaction. We found that the mutant had stronger association with TAP, and, in addition, with tapasin and calreticulin. These data confirm the importance of position 116 for TAP association, and indicate that (1) an aspartic acid at the 116 position can facilitate the interaction, and (2) association with tapasin and calreticulin is affected along with TAP. Furthermore, we tested three natural subtypes of HLA-B15, and found that a B15 subtype with a tyrosine at position 116 (B*1510) was strongly associated not only with TAP, but also with tapasin and calreticulin. In contrast, two B15 subtypes with a serine at position 116 (B*1518 and B*1501) exhibited very little or no association with any of these proteins. Thus, very closely related HLA-B subtypes can differ in regard to interaction with the entire assembly complex. Interestingly, when their surface expression was tested by flow cytometry, the HLA-B15 subtypes with little to no detectable intracellular assembly complex association had a slightly, yet consistently, higher level of the open heavy chain form than did the B15 subtype with intracellular assembly complex association. These data suggest that the relatively low strength or short length of interaction between endoplasmic reticulum proteins and natural HLA class I molecules can decrease their surface stability.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

HLA-DR polymorphism affects the interaction with CD4.

Major histocompatibility complex (MHC) class II molecules are highly polymorphic and bind peptides for presentation to CD4+ T cells. Functional and adhesion assays have shown that CD4 interacts with MHC class II molecules, leading to enhanced responses of CD4+ T cells after the activation of the CD4-associated tyrosine kinase p56lck. We have addressed the possible contribution of allelic polymorphism in the interaction between CD4 and MHC class II molecules. Using mouse DAP-3-transfected cells expressing different isotypes and allelic forms of the HLA-DR molecule, we have shown in a functional assay that a hierarchy exists in the ability of class II molecules to interact with CD4. Also, the study of DR4 subtypes minimized the potential contribution of polymorphic residues of the peptide-binding groove in the interaction with CD4. Chimeras between the DR4 or DR1 molecules, which interact efficiently with CD4, and DRw53, which interacts poorly, allowed the mapping of polymorphic residues between positions beta 180 and 189 that can exert a dramatic influence on the interaction with CD4.

Alleles↗