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At least 109 records · Page 6Linked to original sources
PubMed1986

Amino acid residues 56 to 69 of HLA-A2 specify an antigenic determinant shared by HLA-A2 and HLA-B17.

The mouse monoclonal antibody MA2.1 was previously used to define an epitope shared by native HLA-A2 and HLA-B17 molecules and amino acid sequence comparison of nine HLA-A,B,C molecules identified residues 62 to 65 as the region most likely to form this epitope. An unabsorbed rabbit antiserum raised against a peptide corresponding to residues 56 to 69 of HLA-A2 gives highly specific reactions with HLA-A2 and HLA-B17 heavy chains in Western blots. No interactions with native HLA-A2 and B17 molecules were detected in a variety of assays. Although the topographic relationship between the epitopes recognized by the rabbit antiserum and the monoclonal antibody could not be determined, the results show that residues 56 to 69 of HLA-A2 can form epitopes with specificity for HLA-A2 and HLA-B17.

Amino Acid Sequence↗
PubMed1996

Frequencies of HLA-A24 and HLA-DR4-DQ8 are increased and that of HLA-B blank is decreased in chronic toxic oil syndrome.

The cause of toxic oil syndrome (TOS) has not yet been definitively determined, but some genetic susceptibility factors (certain HLA antigens and female sex) have been identified in 236 patients. Similarities with genetic factors for scleroderma and hydralazine-induced lupus (i.e. in TOS female sex and HLA-A24, Pcorrected = 0.00001 and DR4, Pcorrected = 0.04, respectively) may provide a clue to the responsible xenobiotic and its pathogenesis, and may also help in understanding the basis of the related eosinophilia-myalgia syndrome associated with tryptophan ingestion. In this paper it is also established that a human class I antigen (HLA-A24) and, independently, an HLA class II haplotype (DR4-DQ8, Pcorrected = 0.04) and arginine 52 in the alpha-DQ chains (Pcorrected = 0.03) are associated with TOS susceptibility, similarly to insulin-dependent diabetes. This further supports the classification of TOS as an autoimmune disease. Also, the increased frequency of a particular set of low-frequency HLA class I antigens in chronic TOS patients (i.e. B27, B37, B38 and B49) and the probable decrease in the frequency of HLA-B homozygotes in surviving patients (Pcorrected = 0.008) may provide an objective model to explain the maintenance of the HLA polymorphism: less frequent HLA alleles may be more advantageous in the event of unexpected human contact with unusual xenobiotics (not only microbes); however, other mechanisms working together to preserve and generate HLA polymorphism may coexist.

Fatty Acids, Monounsaturated↗
PubMed1996

A novel method for simultaneous high resolution identification of HLA-A, HLA-B, and HLA-Cw alleles.

We describe a novel high resolution DNA based typing approach for HLA class I alleles, which identifies the recombinational motifs present in exons 2 and 3 of the HLA class I genes. Unique identification patterns for 201 known HLA-A, HLA-B, and HLA-Cw alleles were generated by the use of only 40 probes, which were targeted at these common motifs. The unambiguous identification of the alleles was achieved by the development of a new and powerful allelic separation technique that allows isolation of single alleles after amplification. To validate the method, we have used locus-specific primers to amplify exons 2 and 3 of HLA-A, HLA-B, and HLA-Cw loci from 22 heterozygous and 41 homozygous cell lines. After amplification, the allelic fragments from each locus were separated, blotted, and hybridized with the 40 probes. In all cases, the allelic products could be separated and 81 different class I alleles, 33 HLA-A, 30 HLA-B, and 18 HLA-Cw, were identified according to the predicted probe hybridization patterns.

Alleles↗
PubMed1990

Differential expression of HLA-E, HLA-F, and HLA-G transcripts in human tissue.

The data presented here demonstrate that the HLA-G class I gene is unique among the members of the human class I gene family in that its expression is restricted to extraembryonic tissues during gestation. Furthermore, the pattern of HLA-G expression in these tissues changes as gestation proceeds. During first trimester HLA-G is expressed within the placenta and not within the extravillous membrane. At term, the pattern of the HLA-G expression is reversed, extravillous membrane expresses HLA-G while placenta does not. Another non-HLA-A, -B, -C class I gene, HLA-E, is also expressed by extraembryonic tissues. Unlike HLA-G, HLA-E is expressed by both placenta and extravillous membrane at first trimester and at term. These results raise the intriguing possibility that the HLA-G-encoded molecule has a role in embryonic development and/or the fetal-maternal immune response.

Embryo, Mammalian↗
PubMed2002

Point mutation in the beta sheet of the HLA-C alpha2 domain generates a novel HLA-C allele, HLA-Cw*08012, in a Puyuma Aboriginal individual in Taiwan.

We report herein the identification of a new HLA-C allele using sequence-based typing (SBT). This novel allele, HLA-Cw*08012, was found in an Aboriginal individual from the Puyuma tribe in the southern part of Taiwan. This individual was typed by the SBT method as having an HLA genotype of HLA-A*2402/2402, HLA-B*1502/4801, HLA-Cw*08011/08012, HLA-DRB1*15011/08032, HLA-DRB5*01011, and DPB1*0501/1401. This new allele differs from HLA-Cw*08011 in one of the nucleotides of the polymorphic exon 3 at codon 99 [TAT-->TAC; both code for tyrosine]. This residue is located in the beta sheet of the HLA-C alpha2 domain. This new allele was detected in a few individuals of the Puyuma tribe in Taiwan, but has not yet been observed in other populations in Taiwan.

Alleles↗
PubMed1996

A comparative study of HLA genes in HLA-B27 positive ankylosing spondylitis and HLA-B27 positive peripheral reactive arthritis.

OBJECTIVE: To determine whether HLA-B27 positive patients with ankylosing spondylitis (AS) and reactive arthritis (ReA) share additional HLA factors that confer disease susceptibility. METHODS: HLA class I antigens were typed serologically, and class II antigens molecularly, in samples taken from 33 patients with AS, 30 patients with ReA, and 55 healthy HLA-B27 positive controls. RESULTS: There was no major difference between the HLA alleles in AS and ReA patients, but deviations were observed when compared with healthy controls, especially between the antigens that were probably encoded by genes in the non-B27 chromosome. CONCLUSION: These results suggest that both HLA class I and class II genes may influence the pathogenesis of HLA-B27 positive ReA, whereas class I antigens seem to be the major additional genetic factors in HLA-B27 positive AS.

Adult↗
PubMed2003

HLA-A, HLA-B and HLA-DR matching reduces the rate of corneal allograft rejection.

PURPOSE: The purpose of this study is to determine the effectiveness of HLA typing in preventing corneal allograft rejection. METHODS: This retrospective single-center study analyzed 459 consecutive HLA-typed patients who underwent perforating keratoplasty (PKP) between 1983 and 2001. Grafts were postoperatively transparent after donor-recipient selection by HLA-A, -B and -DR typing. Patients were divided into a low- and a high-risk group based on their preoperative diagnosis. RESULTS: The estimated 1-, 5- and 10-year graft survival (Kaplan-Meier) was 93, 88 and 67% in low-risk patients and 73, 43 and 38% in high-risk patients. We found a significant correlation between the number of HLA mismatches and the rate of allograft rejections: a donor-recipient match of two or more alleles in HLA-A, -B or -DR reduces the rejection rate by at least 10% in low-risk (10 years after PKP; P<0.04) and 40% in high-risk patients (3 years after PKP; P<0.0001). Especially HLA-B mismatches are important prognostic factors for both low- ( P<0.008) and high-risk patients ( P<0.003). Considering both HLA-B and -DR mismatches significantly reduces the rate of allograft rejection, particularly in high-risk patients ( P<0.0001). Matching on a split typing level offers no significant advantage over broad level matching. CONCLUSION: Clinical results confirm theories developed to explain the function of the HLA (MHC) receptor. The closest possible donor-recipient match of HLA antigens based on broad level typing significantly reduces the rate of allograft rejection and thus improves the prognosis for long-term transparency of corneal grafts in both high- and low-risk patients.

Cornea↗
PubMed1990

Distribution of HLA-DR, HLA-DP, HLA-DQ antigens in liver tissue from patients with primary sclerosing cholangitis.

This study describes the distribution of the major histocompatibility class II antigens HLA-DR, HLA-DP, and HLA-DQ in liver tissue from eight patients with primary sclerosing cholangitis, by means of the immunoperoxidase technique on cut cryostat sections. HLA-DR was expressed on the bile duct epithelium and vascular endothelium from all patients. HLA-DP showed an expression much like HLA-DR on the bile duct epithelium, but the vascular endothelium mostly did not stain for HLA-DP. HLA-DQ was generally more weakly expressed, and only three of the patients expressed HLA-DQ on the bile ducts. None of the hepatocytes expressed any of the MHC class II antigens.

Adult↗
PubMed1997

DNA typing of HLA class I (HLA-A) and class II genes (HLA-DR, -DQ and -DP) in Japanese patients with gastric cancer.

Gastric cancer is multifactorial disease and several reports have described genetic factors involved in pathogenesis of gastric cancer. Recently, it was reported that HLA class II gene DQB1*0301 was strongly associated with gastric cancer in Caucasian population (20). We performed DNA typing of HLA class I (HLA-A) and HLA class II genes (HLA-DR, DQ and DP) to elucidate the HLA alleles or HLA haplotypes associated with gastric cancer in Japanese population using polymerase chain reaction-sequence-specific oligonucleotide probe analysis in 88 unrelated patients with gastric cancer and 525 unrelated healthy controls. We observed slight difference in frequencies of some HLA alleles and haplotypes between gastric cancer patients and controls; however, after Bonferroni correction, statistical significance was not confirmed. It is possible that environmental factors such as diet cover the contribution of genetic factors to the disease in Japanese population, which has a higher frequency of gastric cancer than do Caucasian populations, most likely due to more exposure to environmental risk factors.

Adult↗
PubMed2003

Flow cytometric HLA-B27 screening: cross-reactivity patterns of commercially available anti-HLA-B27 monoclonal antibodies with other HLA-B antigens.

BACKGROUND: Some 50 clinical laboratories in the Benelux perform flow cytometric HLA-B27 screening and participate in the Benelux external quality assessment scheme operational since 1995. Results from this scheme indicate that cross-reactivity of HLA-B27 monoclonal antibodies (mAbs) is a major problem. METHODS: We analyzed cross-reactivity patterns of commercially available mAbs for HLA-B27 screening. Three clones of HLA-B27 mAb (ABC-m3, n = 3; FD705; and GS145.2) from five manufacturers were evaluated. Test cells were selected as to express HLA-B antigens with known serologic cross-reactions (HLA-B7, B12, B13, B16, B17, B22, B37, B40, B41, B42, B47, and B48). Cells without B27 cross-reactive antigens (B5, B8, B14, B15, B21, and B35) and cells positive for B27 were included as controls. All tests were performed and interpreted as recommended by the manufacturers. Cross-reactivity was defined as increased fluorescence intensity in comparison with the baseline reactivity observed with the corresponding immunoglobulin G isotype control mAb. RESULTS AND CONCLUSIONS: All mAbs tested showed cross-reactivity, ranging from weak (+/-) to strong (+), with different antigens and different degrees of intensity-ABC-m3: (+/-) B12, B16, B17, B41, B47, and B48 and (+) B7, B13, B22, B37, B40, and B42; GS145.2: (+/-) B13, B17, B22, B40, and B47 and (+) B7, B16, B37, B42, and B48; FD705: (+/-) B12, B13, B16, and B48 and (+) B17, B37, and B47. If one mAb had been used for HLA-B27 screening, ABC-m3 would have yielded nine false-positive B27 assignments, FD705 would have yielded seven, and GS145.2 would have yielded two. This problem largely canbe avoided by the combined use of two different mAb clones. The combination of FD705 and GS145.2 yielded the best results, with one false-positive HLA-B27 assignment among the 99 HLA-B27(-) samples of this highly selected panel.

Antibodies, Monoclonal↗
PubMed2001

HLA-A3 increases and HLA-DR1 decreases the risk of acute graft-versus-host disease after HLA-matched sibling bone marrow transplantation for chronic myelogenous leukaemia.

Frequencies of human leucocyte antigens (HLA)-A, -B and -DR were determined in 751 patients with chronic myelogenous leukaemia (CML) reported to the European Group for Blood and Marrow Transplantation after bone marrow transplantation from HLA-identical family donors and related to the occurrence of graft-versus-host disease (GVHD). HLA-A3 and DR1 were significantly associated with acute GVHD, the first with a higher risk (44% in HLA-A3(+) versus 34% in HLA-A3(-) patients) and the latter with a lower risk (28% in HLA-DR1(+) versus 38% in HLA-DR1(-) patients) for developing acute GVHD grade II--IV. Both factors were independent of known variables for GVHD as shown in a multivariate analysis. The results show that MHC alleles independently influence the incidence of GVHD in bone marrow transplantation from an HLA-identical donor for first chronic-phase CML. Possible mechanisms might include an HLA antigen-specific allele-associated effect, and/or non-specific allele-associated immune hypo- or hyper-responsiveness.

Adolescent↗
PubMed1993

Comparison of the P2 specificity pocket in three human histocompatibility antigens: HLA-A*6801, HLA-A*0201, and HLA-B*2705.

Coordinates from x-ray structures of HLA-A*6801, HLA-A*0201, and HLA-B*2705 were analyzed to examine the basis for their selectivity in peptide binding. The pocket that binds the side chain of the peptide's second amino acid residue (P2 residue) shows a preference for Val, Leu, and Arg in these three HLA subtypes, respectively. The Arg-specific pocket of HLA-B*2705 differs markedly from those of HLA-A*0201 and HLA-A*6801, as a result of numerous differences in the side chains that form the pocket's surface. The cause of the specificity differences between HLA-A*0201 and HLA-A*6801 is more subtle and depends both on a change in conformation of pocket residue Val-67 and on a sequence difference at residue 9. The Val-67 conformational change appears to be caused by a shift in the position of the alpha 1-domain alpha-helix relative to the beta-sheet in the cleft and may, in fact, depend on amino acid differences remote from the P2 pocket. Analysis of the stereochemistry of the P2 side chain interacting with its binding pocket permits an estimate to be made of its contribution to the free-energy change of peptide binding.

Amino Acid Sequence↗
PubMed1995

HLA-A0201 and HLA-B7 binding peptides in the EBV-encoded EBNA-1, EBNA-2 and BZLF-1 proteins detected in the MHC class I stabilization assay. Low proportion of binding motifs for several HLA class I alleles in EBNA-1.

B lymphocytes immortalized with EBV in vitro, lymphoblastoid cell lines (LCL), express eight EBV-encoded proteins, EBV nuclear antigens -1 to -6 (EBNA-1 to -6), and latent membrane proteins 1 and 2 (LMP 1 and 2). After appropriate stimulations of blood lymphocytes from seropositive individuals, MHC-restricted cytotoxic T cells (CTL), which lyse LCL cells, can be generated in vitro. Such CTLs can recognize EBNA-2 to -6, and LMP 1 and 2, but not EBNA-1-derived peptides presented on the cell surfaces. We posed the question whether this exceptional feature of EBNA-1 is due to lack of MHC class I binding peptides. A computer search for 11 human leukocyte antigen (HLA) alleles showed that EBNA-1 has a lower number and lower proportion of relevant binding motifs to several alleles than EBNA-2 to -6 and LMP 1 and 2. The low motif numbers in EBNA-1 is in line with its apparent failure to generate a CTL response, and it may be the consequence of immunoselection allowing the existence of EBV genome-carrying B cells in the immunocompetent hosts. The binding capacities of synthetic peptides of EBNA-1 and -2 and of the immediate early lytic cycle protein BZLF-1 to HLA-A0201 (A2) and HLA-B7 molecules were tested in an MHC stabilization assay. The peptide transporter-deficient T2 line, which expresses a low level of HLA-A2 and its HLA-B7 transfectant subline, were used for this purpose because specifically bound peptides elevate the surface expression of these MHC molecules. Of five synthetic nonamer EBNA-1 peptides which include the relevant binding motif, four bound to A2. In a series of 20-amino acid-long overlapping EBNA-1 peptides none showed binding to A2, while eight peptides bound to B7. Two 20-amino acid-long EBNA-2 and seven BZLF-1 peptides were identified as A2 binders, and four EBNA-2 and eight BZLF-1 peptides bound to B7. Thus, we have exclude the possibility that the inability of the EBNA-1 protein to generate HLA-restricted CTLs could be due to the lack of HLA class I binding peptides in its sequence. The finding that several EBNA-1 peptides could bind to these two HLa molecules does not, however, necessarily reflect the natural situation because the peptides may not be processed and/or transported to the cell surfaces. We have stimulated lymphocytes of healthy donors with relevant HLA types with the autologous LCL.(ABSTRACT TRUNCATED AT 400 WORDS)

Alleles↗
PubMed2006

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↗
PubMed1992

Cloning and physical mapping of the HLA class I region spanning the HLA-E-to-HLA-F interval by using yeast artificial chromosomes.

The HLA class I genes are located within a 2-million-base pair (2-Mbp) region constituting the telomeric half of the human major histocompatibility complex. The large majority of the class I sequences, including the HLA-A, -E, -F, and -G genes, is found within the telomeric 1 Mbp. We report here the isolation and characterization of yeast artificial chromosome (YAC) clones that span a contiguous region of greater than 1.2 Mbp and include 14 of the 18 characterized class I sequences. Restriction enzyme mapping and the use of locus-specific probes have allowed all of the class I genes and sequences to be ordered and positioned within the region. In addition, the transcriptional orientation of the four class I genes has been determined. Using probes derived from the ends of YAC inserts and from class I pseudogenes, we describe a highly polymorphic region between the HLA-A and HLA-G genes. This region appears to be deleted in certain HLA haplotypes, shortening the distance between HLA-A and HLA-G by greater than 50 kilobase pairs (kbp). As part of the characterization of the YAC clones, unique sequence probes derived from the ends of each YAC insert were identified. When combined with probes derived from HLA genes and pseudogenes, 25 locus-specific probes spanning the 1.2-Mbp region have been identified for an average of 1 probe every 48 kbp.

Chromosomes, Fungal↗
PubMed2000

[Frequency of HLA-A, HLA-B and HLA-Cw antigens in the Slovak population].

Results on HLA-A, -B and -Cw antigen frequencies in the Slovak population are presented. HLA-A, -B, -Cw antigens were determined in 654 healthy unrelated individuals. The highest frequency was observed for the antigens HLA-A2, -A1; HLA-B12, -B35, and HLA-Cw8. The least frequent antigens were HLA-A34, -A36, HLA-B58, -B67, -B70, -B77, and HLA-Cw8. The results were compared with those of the previous study and with those of Czech, Austrian and Hungarian populations. No statistically significant differences were observed. (Tab. 5, Fig. 2, Ref. 9.)

Gene Frequency↗
PubMed2002

Point mutation in the alpha helix of the HLA-C alpha2 domain generates a novel HLA-C allele,HLA-Cw*0106, in a Han Chinese individual in Taiwan.

We report herein the identification of a new HLA-C allele using sequence-based typing (SBT). This novel allele, HLA-Cw*0106, was found in a Han Chinese individual from Taiwan. This individual was typed using SBT as having a class I HLA genotype of HLA-A*0206/0207, HLA-B*4601/5601, and HLA-Cw*0102/0106. This new allele differs from HLA-Cw*0102 in one of the nucleotides of the polymorphic exon 3 at codon 152 (GAG-->GTG; E152V). This residue is located in the alpha helix of the HLA-C alpha2 domain and may have the potential to affect the binding of HLA-C molecules with antigenic peptides and/or the interactions with the T cell receptor. This new allele was detected in a few individuals of Han Chinese in Taiwan, but has not yet been observed in the aboriginal populations in Taiwan.

Asian People↗
PubMed1990

Self-tolerance to HLA focuses the response of immunized HLA-transgenic mice on production of antibody to precise polymorphic HLA alloantigens.

HLA class I-transgenic mice express HLA antigen on their tissues and establish self-tolerance to the expressed monomorphic and polymorphic determinants. When challenged with skin grafts and lymphoid cells of a second HLA-transgenic mouse expressing a different HLA molecule, a specific immune response is elicited that is focused on the determinants specified by the allelic HLA differences between donor and recipient transgenic mice. In the studies described, this has led to the production of a number of monoclonal antibodies with specificity for the HLA-Cw3 and HLA-B7 crossreactive groups of class I antigens. These results indicate that immunization of appropriate transgenic strains of mice with murine cells expressing a different HLA allelic transgene should permit the generation of monoclonal antibodies of narrow specificity against virtually any polymorphic epitope on HLA antigens.

Animals↗