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Biomedical subjects

A Wakisaka

Publications and source records attributed to A Wakisaka.

At least 91 records · Page 5Linked to original sources
PubMed1987

Role of HLA-DR antigens in Japanese patients with sarcoidosis.

Fifty-three Japanese patients with sarcoidosis were tested for HLA-A,B,C, DR, and DQ antigens in order to investigate immunogenetic mechanisms in the pathogenesis of sarcoidosis. All of the patients had abnormal shadows on their chest radiographs, and all had histologically confirmed sarcoidosis. Groups of 60 and 57 unrelated Japanese served as control subjects for HLA-A,B,C and HLA-D region antigens, respectively. The frequency of HLA-DRw52 was 79.2% (42 of 53) in the patient group compared with 50.9% (29 of 57) in the control group, and the difference was significant (chi 2 = 9.66, p less than 0.005, pc less than 0.05, relative risk = 3.69). On the other hand, no significant association was found with HLA-A,B,C antigens. When various clinical features of the patients were taken into account, there was a tendency for the frequency of DRw52 to be lower in the patients who were in an advanced stage or who had resisted treatment with steroids. Furthermore, 31 of the 32 patients without ophthalmic involvement were DRw52-positive, which was highly significant (96.9% as compared with 50.9% of the control group; chi 2 = 19.74, p less than 0.001, pc less than 0.01, relative risk = 29.93), whereas the frequency of DRw52 in the patients with ophthalmic involvement was almost the same as in the control group. These results suggest that HLA-DR antigens play a significant role in the pathogenesis of sarcoidosis, and there may be a heterogeneity in the clinical entity of sarcoidosis.

Adolescent↗
PubMed1986

A study on class II antigens involved in the T cell proliferative responses to PPD using cross-reacting monoclonal antibodies in human and murine system.

Two monoclonal antibodies (MoAb) 1E4 and ISCR3, which detect class II antigens across species barriers, were studied for their inhibitory effects on human and murine T cell proliferative responses to purified protein derivative of tuberculin (PPD). The 1E4 detected at least a polymorphic determinant on I-A molecules from mice carrying the H-2b haplotype, and the ISCR3 detected the Ia.7 determinant on I-E molecules. Nevertheless, both 1E4 and ISCR3 recognized monomorphic determinants on HLA-DR antigens (human I-E equivalent molecules), but not on HLA-DQ antigens (human I-A equivalent molecules). It was demonstrated that 1E4 significantly inhibited PPD-specific responses of T cells from Ib-bearing mice. In contrast, ISCR3 showed marginal effects on the responses of mice bearing Ia.7. However, in the human system both 1E4 and ISCR3 reduced proliferative responses to PPD. These results suggest that a functional difference exists between humans and mice in the I subregion products involved in the T cell proliferative responses to PPD.

Animals↗
PubMed1986

Public determinants of HLA indicated by pregnancy antibodies.

A tentative table of public specificities in the HLA-A and -B loci is provided. It is based on an all-inclusive survey of placenta extracts from 50,000 pregnancies. We postulate that most of the specificities found are directed against public epitopes. In support of this postulate are the facts that certain combinations occur very frequently, monoclonal antibodies have been made to some of the epitopes, and some have already been established by absorption experiments as being a single specificity. The immunogenicity score for each private and public specificity was computed by taking into account the chance of immunization. It was shown that immunogenicity can vary by factors of more than ten between different specificities. Significantly, immunogenicity of the public epitopes was just as high as against the private ones. This indicates that the public epitopes should be considered as independent, separate antigens in transplantation. Establishment of a table of public specificities and the recognition of each by international nomenclature would be the first step in evaluating public epitopes for transplantation matching.

Antilymphocyte Serum↗
PubMed1985

Partial N-terminal sequence analysis of human class II molecules expressing the DQw3 determinant.

HLA-DQ molecules were isolated from DRw9-homozygous and DR4-homozygous cell lines by using a monoclonal antibody HU-18, which recognizes class II molecules carrying the conventional DQw3 determinant. The partial N-terminal sequence analysis of the DQw3 molecules revealed that they have sequences homologous to those of murine I-A molecules. Within the limits of our sequence analysis, the DQw3 molecules from the two cell lines are identical to each other in both the alpha and beta chains. The DQ alpha as well as DQ beta chains were found to have amino acid substitutions when compared to other I-A-like molecules whose sequences have been reported. These differences may contribute to the DQw supertypic specificity. The polymorphic nature of DQ molecules is in marked contrast to that of DR molecules where DR alpha chains are highly conserved while DR beta chains have easily detectable amino acid substitutions.

Amino Acid Sequence↗
PubMed1985

Electrophoretic analysis of HLA-DR2 molecules isolated from HLA-Dw2 and HLA-Dw12 cell lines.

To answer the question of whether or not polymorphism exists among HLA-DR2 molecules derived from cells homozygous for HLA-DR2, but expressing different HLA-D specificities, HLA-DR2 molecules were isolated from HLA-Dw2 and HLA-Dw12 homozygous cells using a monoclonal antibody operationally monospecific for HLA-DR2, and were compared to each other by two-dimensional gel electrophoresis. No electrophoretically discernible polymorphism was found in either the heavy or the light chain subunits of the HLA-DR2 molecules. These findings are in marked contrast with previous observations that each of the HLA-DR4-associated HLA-D clusters expresses an electrophoretically distinct HLA-DR4 light chain.

Antibodies, Monoclonal↗
PubMed1985

Effect of HLA on the cellular immune response to varicella-zoster virus.

The effect of HLA on varicella-zoster virus (VZV)-specific lymphocyte transformation (LTF) was studied in 100 normal immune adults and 64 children who were immunized with live attenuated varicella vaccine. In the normal adults, a statistically significant association was observed between low responsiveness and the presence of A2 (p less than 0.025), and also between high responsiveness and the presence of Aw24 (p less than 0.05). A similar but clearer association, i.e. low responsiveness with A2 (p less than 0.005) and high responsiveness with Aw24 (p less than 0.025), was observed in the vaccinated children. In these children, Aw31 was also found to be related to low responsiveness (p less than 0.05). These results suggest that the VZV-specific cellular immune response is in some way influenced by HLA.

Adult↗
PubMed1985

Demonstration of structural polymorphism among MB3 light chains by two-dimensional gel electrophoresis.

The heavy and light chain subunits of MB3 molecules were isolated from KT2 (DKT2, DR4, MB3 homozygous), ER (Dw4, DR4, MB3 homozygous), JMe (Dw5, DR5, MB3 homozygous), EBV-Sh (DSh, DRw6.2, MB3 homozygous), and EBV-Ky (DKy, DRw9, MB3 homozygous) cells and were compared with one another by two-dimensional gel electrophoresis. The MB3 light chains from KT2, ER, and EBV-Ky cells were clearly different in terms of their isoelectric points, whereas those from ER, JMe, and EBV-Sh cells were indistinguishable. No differences in charge or m.w. were noted for the MB3 heavy chains from the five cell lines. Thus, three out of the five MB3-positive, D/DR-disparate cell lines were found to express structurally distinct MB3 molecules, demonstrating that MB3 is a public serologic specificity shared by at least three structurally distinct MB (human I-A-like) molecules. Because the DR light chain subunits isolated from EBV-Wa, KT2, ER, JMe, EBV-Sh, and EBV-Ky cells differed from one another in their isoelectric points, the DR light chains were apparently more polymorphic than the MB3 light chains.

B-Lymphocytes↗
PubMed1984

Evidence for polymorphism of MB3 antigens among three HLA-D clusters associated with HLA-DR4.

In a previous study, we showed that the three hitherto serologically indistinguishable HLA-D specificities associated with HLA-DR4, HLA- DYT , HLA- DKT2 , and HLA-Dw4 can be distinguished on the basis of their reactivity with two distinct Ia-like-specific monoclonal antibodies, HU-18 and HU-23. In this study, we attempted to identify and characterize Ia-like molecules recognized by HU-18 and HU-23 on a molecular level because Ia subsets (HLA-DR, MB, MT, or SB) identified by them remained unknown. The results of sequential coprecipitation assays and two-dimensional gel analyses showed that both HU-18 and HU-23 recognize antigenic determinants borne on MB3 but not on HLA-DRw6.2 molecules. Because the two monoclonal antibodies, specific for determinants carried on MB3 molecules, show distinct reactivity against homozygous typing cells defining HLA- DYT , HLA- DKT2 , and HLA-Dw4, all of which share DR4- MB3 , the data indicate that these three HLA-D clusters associated with HLA-DR4 possess distinct MB3 molecules, suggesting the existence of polymorphism in MB3 antigens.

Antibodies, Monoclonal↗
PubMed1984

Characterization of sialosylated Lewisx as a new tumor-associated antigen.

A monoclonal antibody CSLEX1 which reacts with sialosyl Lex but not with sialosyl Lea has been produced. The CSLEX1 antigen has a tissue distribution similar to that of Lex, appearing characteristically in the proximal tubules of the kidney and on granulocytes. It is tumor associated in that 14 of 34 (41%) of tumor lines tested reacted with the CSLEX1 antibody, and 50 of 74 (68%) of tumor tissues tested reacted with the antibody. Loss of immunoperoxidase staining of tissues after neuraminidase treatment showed that the antibody is reacting to sialyl derivatives. The antibody reacted in solid-phase radioimmunoassay to sialosyllactofucopentaosyl(III)ceramide and sialosyldifucosylganglioside (6B). These results indicate that the CSLEX1 epitope has the following structure: (formula: see text) This structure had not previously been known to be tumor associated.

Antibodies, Monoclonal↗
PubMed1983

Serologic dissection of HLA-D specificities by the use of monoclonal antibodies. II. Distinction between HLA-Dw2 and HLA-Dw12.

Three cytotoxic monoclonal antibodies, HU-11, HU-32, and HU-33, specific for human Ia-like antigens were used to analyze the two HLA-DR2-associated HLA-D specificities, HLA-Dw2 and HLA-Dw12. In the HLA-Dw2, DR2, MB1 homozygous B-cell line EB-CMG, the binding of radiolabeled HU-32 and HU-33 was strongly inhibited by the addition of nonlabeled HU-11, whereas no inhibition occurred in the HLA-Dw12, DR2, MB1 homozygous B-cell line EB-KT. To confirm this differential inhibition pattern further, F(ab')2 fragments were prepared from HU-11, and their ability to inhibit complement-dependent lysis mediated by HU-32 and HU-33 was assessed against a total of five homozygous typing cell lines homozygous for HLA-Dw2, DR2, MB1 or HLA-Dw12, DR2, MB1, including EB-CMG and EB-KT. Here again, the same differential inhibition pattern as that observed in the radiobinding inhibition assays was obtained. Thus, the data suggest that the two kinds of HLA-DR2-positive homozygous typing cell lines with distinct HLA-D specificity can be distinguished from each other by using solely serologic methods. This is the first clear-cut serologic distinction made between homozygous typing cells defining HLA-Dw2 and those defining HLA-Dw12, since no serologic means that enables one to distinguish one from the other has been available.

Antibodies, Monoclonal↗
PubMed1983

Serologic dissection of HLA-D specificities by the use of monoclonal antibodies.

To study the gene products of the HLA complex, we produced two monoclonal antibodies, termed HU-18 and HU-23. They were active in complement-dependent cytotoxicity and detected B-cell alloantigens encoded by a locus (or loci) linked to HLA. When three types of HLA-DR4 homozygous B-cell lines with different HLA-D specificities were tested for reactivity with HU-18 and HU-23, they displayed distinct reaction patterns depending on the HLA-D specificities they possessed: EBV-Wa (HLA-DYT homozygous), negative for both HU-18 and HU-23; KT2 and KOB (HLA-DKT2 homozygous), positive only for HU-18; and ER (HLA-Dw4 homozygous), positive for both. These differential reaction patterns were further confirmed by testing against a panel of 17 HLA-DR4-positive peripheral blood lymphocytes with known HLA-D specificities. Thus, these monoclonal antibodies allow us to identify HLA-DYT, HLA-DKT2, and HLA-Dw4 solely by serologic methods. This is the first clearcut serologic identification of these three HLA-DR4-associated HLA-D specificities, which have been indistinguishable by conventional serology and identified only by cellular techniques. It is hoped that immunochemical investigations using HU-18 and HU-23 will advance our understanding of the HLA-D region on a molecular level.

Antibodies, Monoclonal↗
PubMed1983

A monoclonal antibody that detects a polymorphic determinant common to HLA-DR1 and 2.

In an attempt to study the gene products of the HLA complex, a monoclonal antibody, named HU-30, was produced by immunizing BALB/c mice with a cultured human B lymphoblastoid cell line, Shi-C3 (Aw24, Aw31, Bw51, Bw52, DR2, DR blank, MT1, MT2, MB3). HU-30 belonged to the IgG2 subclass and was active in complement dependent cytotoxicity. When the serological specificity was evaluated with a panel of 15 cultured human lymphoblastoid cell lines, it was found that HU-30 detected a polymorphic determinant, common to HLA-DR1 and 2, with much stronger cytotoxic activity against HLA-DR2 positive B cell lines. When HU-30 was tested against a panel of B cells from 84 healthy donors at a dilution of 2(-13), it gave positive reactions only with cells typed as HLA-DR2. Furthermore, sequential coprecipitation studies indicated that the HU-30 determinant was borne on the molecules carrying the HLA-DR determinants. Thus, HU-30 appears to be of great value as a tissue typing reagent monospecific for HLA-DR2.

Animals↗