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P Ivanyi

Publications and source records attributed to P Ivanyi.

At least 55 records · Page 3Linked to original sources
PubMed1988

Nucleotide sequences of chimpanzee MHC class I alleles: evidence for trans-species mode of evolution.

To obtain an insight into the evolutionary origin of the major histocompatibility complex (MHC) class I polymorphism, a cDNA library was prepared from a heterozygous chimpanzee cell line expressing MHC class I molecules crossreacting with allele-specific HLA-A11 antibodies. The library was screened with human class I locus-specific DNA probes, and clones encoding both alleles at the A and B loci have been identified and sequenced. In addition, the sequences of two HLA-A11 subtypes differing by a single nucleotide substitution have been obtained. The comparison of chimpanzee and human sequences revealed a close similarity (up to 98.5%). The chimpanzee A locus alleles showed greatest similarity to the human HLA-A11/A3 family of alleles, one of them being very close to HLA-A11. Similarly, segments of the ChLA-B alleles displayed greatest similarity to certain HLA-B alleles. The calculated evolutionary branch point for the A11-like alleles is 7 x 10(6) to 9 x 10(6) years, whereas the other A locus alleles diverged between 12 x 10(6) and 17 x 10(6) years ago. Since the human and chimpanzee lineages separated 5 x 10(6) to 7 x 10(6) years ago, our data support the notion that during evolution, MHC alleles are transmitted from one species to the next.

Alleles↗
PubMed1988

Immunological function of HLA-C antigens in HLA-Cw3 transgenic mice.

The human major histocompatibility complex encodes three classical class I antigens, HLA-A, -B, and -C. Of these HLA-A and -B act as strong transplantation antigens and as restriction molecules for recognition of foreign antigen by cytotoxic T lymphocytes. In contrast, little is known about HLA-C and it is not clear whether HLA-C has the same functional properties as HLA-A and -B. Transgenic C57BL/6 mice expressing the HLA-Cw3 gene were established. Functional studies demonstrated that transgenic skin was rapidly rejected by normal C57BL/6 mice and that cytotoxic T lymphocytes generated by immunization of the Cw3 transgenic mice with influenza and Sendai virus were restricted by the Cw3 molecule. These data suggest that HLA-Cw3 has immunological functions comparable to those of HLA-A and -B.

Animals↗
PubMed1988

Different linkage disequilibria of HLA-B27 subtypes and HLA-C locus alleles.

Subtypes of HLA-B27 have been identified by cellular, serological and biochemical techniques. Comparison of the various B27 subtype designations showed the existence of seven B27 subtypes. The new WHO nomenclature (1987) of the B27 subtypes is included. We further report on different linkage disequilibria (ld) of the B27 subtypes. In Caucasoids, the prevalent subtype B27.5 is in ld with Cw1 and Cw2, whereas B27.2 is linked only with Cw2. In Orientals, the most frequent subtypes B27.4 and B27.6 usually occur with Cw3 or Cw blank; B27.5 mostly occurs with Cw2, and B27.2 is almost absent.

Alleles↗
PubMed1987

Induction of H-2-specific antibodies by injections of syngeneic Sendai virus-coated cells.

The capacity of the B cell immunoglobulin receptor to recognize complexes of Sendai viral and H-2b antigens was investigated by studying the antibody response to injections of syngeneic Sendai virus-coated (SV+) spleen cells in C57BL/6 (B6) mice. Almost all mice produced alloreactive anti-H2 lymphocytotoxic antibodies. In contrast, such antibodies were found very exceptionally in mice injected with normal (SV-) cells or with Sendai virus (SV) only. The reaction pattern of the cytotoxic antibodies induced was variable and ranged from almost anti-private to widely cross-reactive serotypes. The results of reactions on H-2-congenic, -recombinant and -mutant mouse strains, and of capping and immunoprecipitation experiments showed that the cytotoxic antibodies were directed against H-2 class I molecules. The anti-H-2 antibodies exhibited enhanced binding for SV+ target cells, but absorption experiments showed that this was not the result of cross-reactions with cell surface Sendai viral determinants or with a molecular complex of H-2 plus SV. This conclusion was supported by the observation that syngeneic SV+ cells were not the predominant targets for the induced lymphocytotoxic antibodies. Our results do not support the existence of MHC-restricted antiviral antibodies, but show the induction of anti-class I H-2 alloantibodies by injections with syngeneic SV-coated cells. We present a model for regular induction of anti-H-2 antibodies without intentional alloimmunization.

Animals↗
PubMed1987

Conventional alloantisera can recognize the same HLA-B27 polymorphism as detected by cytotoxic T lymphocytes.

Subtypes of B27 have been identified by cytotoxic T lymphocytes, biochemistry, molecular biology, and murine monoclonal antibodies. In the present study we describe seven B27 subtype-specific pregnancy sera. The reaction pattern of these B27 subtype-specific sera closely parallels the recognition pattern of B27 subtype-specific cytotoxic T lymphocytes. Because the complete amino acid sequence of the studied B27 subtypes (B27W, B27K, B27C, B27D) is known, it can be determined which amino acid substitutions are responsible for recognition by subtype-specific sera and by cytotoxic T lymphocytes, respectively. It is proposed that B27 subtype-specific sera and B27 subtype-specific cytotoxic T lymphocytes recognize the same epitopes or that a single amino acid change can induce multiple antigenic determinants, which are recognized differentially by antibodies and T cells.

Amino Acid Sequence↗
PubMed1987

Monomorphic anti-HLA monoclonal antibody (W6/32) recognizes polymorphic H-2 heavy-chain determinants exposed by association with bovine or human but not murine beta 2-microglobulin.

W6/32 is a mouse anti-HLA class I monoclonal antibody (MoAb) of BALB/c (H-2d) origin with a monomorphic reaction pattern on human cells. In this study, we explain that the previously reported (Ivanyi D et al., Immunogenetics 20:6gg, 1984) cross-reactions of W6/32 with the H-2Db antigen are completely dependent on the formation of a complex between the H-2Db heavy chain with bovine beta 2-microglobulin (beta 2m) from the culture medium. M0Ab W6/32 cross-reacted with various H-2 class I antigens only in the presence of bovine or human beta 2m but not in the presence of beta 2m from other species (goat, sheep, rabbit) or syngeneic mouse beta 2m. The exposure of the W6/32 determinant on mouse cells was dependent on the concentration of human or bovine beta 2m and was influenced by the temperature and time of incubation. The reaction pattern of W6/32 on a large panel of mouse strains showed that the binding is due to at least two critical factors: (i) the H-2 haplotype of the target cells; and (ii) the substitution of murine beta 2m for bovine or human beta 2m. These results show that exposure of a polymorphic class I determinant is dependent on the species origin of beta 2m with which the heavy chain is complexed. Comparison of beta 2m amino acid sequences from various species does not give a clear answer about the shared quality of human and bovine beta 2m. One amino acid position (89) was identified at which human and bovine beta 2m are identical but differ from all other known beta 2m sequences.

Animals↗
PubMed1987

Distribution of HLA-B27 subtypes in patients with ankylosing spondylitis: the disease is associated with a common determinant of the various B27 molecules.

HLA-B27 subtypes can be defined by cellular, serological, and biochemical techniques. The seven subtypes so far identified represent structural variants of B27 with limited variations in the amino acid sequence of the B27 molecule. The routinely typed B27 'antigen' remains a common (shared, public) determinant present on various B27 molecules. The distribution of the subtypes varies strongly among different ethnic groups and they occur in different linkage disequilibria. In the healthy Dutch population only two subtypes were found: B27W (B27 X 1, B27M2+) (90%) and B27K (B27 X 2, B27M2-) (10%). A similar distribution of B27 subtypes was observed in 91 unrelated Dutch patients with ankylosing spondylitis (AS)--namely, 92% B27W and 8% B27K. In Oriental populations the subtype distribution is quite different: B27W occurs in less than 50%, whereas more than 50% individuals are of the B27C and B27D subtypes. Preliminary data indicate that the distribution of subtypes in healthy and diseased Oriental individuals is similar. These results suggest that the B27 and disease (AS) association is not correlated with the structural variations of one of the B27 subtypes, but with a common B27 determinant shared by various B27 subtypes. Consequently, the disease is older than the B27 variants. Further studies on disease and subtype distribution in various ethnic groups might contribute to a better understanding of the origin of both.

Asian People↗
PubMed1986

Evidence for a regulatory role of the T8 (CD8) antigen in antigen-specific and anti-T3-(CD3)-induced lytic activity of allospecific cytotoxic T lymphocyte clones.

The functional role of the T8 antigen of human T cells was studied by inhibition with anti-T8 monoclonal antibodies (mAb) of the cytotoxic action of T8+ cytotoxic T lymphocyte clones (CTL). All clones were allospecific and directed against HLA-B7. The ability of seven different anti-T8 mAb to inhibit the cytotoxicity of these alloreactive CTL clones corresponded with their avidity for a particular target cell. The lysis of cross-reactive antigen-bearing target cells was more readily blocked by anti-T8 mAb than lysis of the specific B7 target cell against which a clone was raised. The seven anti-T8 mAb showed a spectrum of CTL blocking ability ranging from strong blocking with all five CTL clones tested to weak inhibition of only two out of five clones. mAb inhibition of CTL reactivity and cold target inhibition studies with one of the five CTL clones indicate a post-binding role of the T8 molecule. Functional epitope mapping based on CTL blocking with the anti-T8 mAb resulted in the definition of one nonfunctional epitope on the T8 molecule which is only expressed on mature T lymphocytes and a cluster of closely related functional epitopes expressed on both thymocytes and mature T lymphocytes. Not only allospecific cytotoxicity, but also nonspecific cytotoxicity induced anti-T3 mAb in these allospecific clones was inhibited by anti-T8 mAb in the absence of HLA class I expression on the target cell (Daudi cell line). The hierarchy of blocking with anti-T8 mAb and the classification of functional epitopes on T8 in anti-T3-induced nonspecific cytotoxicity were similar to those obtained in blocking of allospecific reactivity of the CTL clones. This analogy points to an identical function of the T8 antigen in both allospecific and anti-T3-induced nonspecific cytotoxicity. If HLA class I molecules are the counter structures of the T8 antigen, then these results argue against an adhesion-like function of the T8 structure. The combined results show that the T8 molecule has a regulatory role in CTL activation. It is postulated that the T8 antigen might serve as a receptor that transduces a negative feedback signal for T cell activation which prevents T cell triggering by nonspecific interaction.

Antibodies, Monoclonal↗
PubMed1986

Individual differences in the cytotoxic T-lymphocyte response in man to public HLA determinants.

The allospecific anti-HLA response of cytotoxic T lymphocytes (CTL) from 22 unrelated individuals and 7 monozygous twin pairs was examined. From each responder, CTL were generated in several responder-stimulator combinations, each mismatched for one HLA-A or -B antigen. The CTL were assayed in the cell-mediated lympholysis (CML) on panels of third-party target cells, comprising cells that express the stimulating antigen (specific target cells), cells that express an antigen cross-reactive with the stimulating antigen (CREG target cells), and cells that do not express either the stimulating or a cross-reactive antigen (nonsharing target cells). Individual variations in the allo-CTL response were observed. We identified individuals (responders) who showed a consistently narrow CTL response and those who showed a broad reaction pattern to various stimulator cells. The narrow response was restricted almost entirely to specific target cells; the broad response comprised lysis of specific, CREG, and nonsharing target cells. These differences were evidently not dependent on the HLA-A, -B, -C phenotype of the responder, because HLA-A, -B, (-C)-identical individuals responded differently to the same stimulator. The identical response of monozygous twins indicates that the allogeneic CTL response is genetically controlled. The CTL response is not regulated by the HLA-DR antigens of the responder, nor is it influenced by the DR mismatch between responder and stimulator. The observed differences were not dependent on sex or age and could not be explained by differences in the T-lymphocyte subsets (OKT3+, OKT4+, OKT8+) or by differences in proliferative reactivity to mitogens (phytohemagglutinin, concanavalin A, phorbol-myristate acetate, pokeweed mitogen, anti-T3 monoclonal antibodies). The IL-2 activity in the supernatants of mixed lymphocyte cultures of broad and narrow responder-stimulator combinations did not differ.

Female↗
PubMed1986

Blind confirmation in Leiden of Geczy factor on the cells of Dutch patients with ankylosing spondylitis.

A follow-up blind study, of the ability of "cross-reactive" antisera to distinguish between the cells of Dutch patients with ankylosing spondylitis (AS) and normal controls, was performed in Leiden. Of the 45 cell samples tested, 29 were fresh peripheral blood mononuclear (PBM) cells while 15 were cryopreserved PBM. No false positives but one false negative was identified among the 45 samples, and the "negative" was confirmed after the recoded cryopreserved cells from this patient were retested. It is concluded that the "cross-reactive" antisera raised in Sydney give good discrimination between patients and normals. Factors affecting the success of the 51Cr-release cytotoxicity assay, and possible reasons for the failure of others to confirm these observations, are briefly discussed.

Antigens, Surface↗
PubMed1983

Biochemical analysis of variant HLA-B27 antigens.

Biochemical analysis of HLA-B27 antigens from individuals that are HLA-ABC identical by serology but distinct in CML typing establishes that two types of HLA-B27 can be defined biochemically. The division of HLA-B27 into a W type and a K type by CML typing correlates perfectly with the biochemical data. HLA-B27 K type possesses a more basic isoelectric point than HLA-B27 W type. Neuraminidase digestions of immunoprecipitated HLA-A,B antigens establish that the difference in isoelectric point between HLA-B27 K and HLA-B27 W is not due to differences in sialic acid content.

Electrophoresis, Polyacrylamide Gel↗
PubMed1982

Human Ia molecules carrying DC1 or BR4X7 determinants are not homologous to murine I-E molecules.

An anti-I-Ek alloantiserum was shown to react with purified human Ia preparation. All Ia preparations tested were actively bound irrespective of their HLA-DR phenotypes. However, from a quantitative point of view, DR7 molecules were significantly less reactive. No reaction was observed with isolated Ia subunits. Only molecules carrying DR determinants, but not those carrying either DC1 or BR4X7 determinants, were bound.

Animals↗
PubMed1982

In vitro-isolated human cytotoxic T-lymphocyte clones detect variations in serologically defined HLA antigens.

T cells of two donors, JR (HLA-A23,29;B7,7;C-;DRw5) and HG (HLA-A2,23;B40,w44;Cw4), were stimulated with cells from an HLA homozygous lymphoblastoid cell line JY (HLA-A2,2;B7,7,C-,DRw4,6) and cloned by limiting dilution after the third stimulation. Two cytotoxic T-cell (CTL) clones, JR-2-16 (from donor JR) and HG-31 (from donor HG), were used for detailed studies. The results of a panel study using lymphocytes from HLA-typed individuals and a study with two HLA recombinant families indicate that the antigens recognized by the CTL clones JR-2-16 and HG-31 were highly associated with HLA-A2 and HLA-B7, respectively. Blocking studies with a monoclonal antibody recognizing a framework determinant on HLA-A, -B and -C antigens and a monoclonal antibody reacting with HLA-A2 support the notion that JR-2-16 and HG-31 interact with the HLA-A2 and the HLA-B7 antigens per se. However, these clones did not recognize the HLA-A2 and HLA-B7 of all donors typed for these antigens, suggesting that the HLA-A2 and HLA-B7 antigens of these particular donors are variants of the serologically defined HLA antigens. These results indicate that in vitro-derived human CTL clones detect variations in the serologically defined allospecificities and can be used as reagents to elucidate the polymorphism of HLA antigens further.

Antibodies, Monoclonal↗
PubMed1982

Subtypes of HLA-B27 detected by cytotoxic T lymphocytes and their role in self-recognition.

In the present study cytotoxic T lymphocytes were generated in MLC of lymphocytes from two unrelated HLA-A, B, C-identical, B27-positive, but D/DR-different, individuals. These CTL were shown to detect subtypes of HLA-B27. CTL specific for influenza virus lysed infected target cells matched for HLA-B27 only when they shared the same subtype. This indicates that the two subtypes of HLA-B27 detected by CTL function also as distinct elements in a self-restricted CTL response. Both subtypes were found among patients with ankylosing spondylitis.

Cytotoxicity, Immunologic↗
PubMed1980

Unexpected lympho-cytotoxic reactions of anti-H-2 sera on normal lymph-node cells: are they due to altered H-2 structures or anti-viral antibodies?

When testing the serum of an individual anti-H-2 immunized mouse (B10 x A.SW)F1 anti-B10.M by the routine micro-lymphocytotoxicity test on lymph-node cells, unexpected antibodies were found. The most striking finding was that after absorption of anti-H-2.8 antibodies with B10.A(2R) (Kk) cells, antibodies remained which reacted with AKR, B10.AKM and B10.A V+ mice while B10.A V-, B10.BR and C3H mice were negative. While all these strains share the Kk allele, only the positively reacting strains express high titres of infectious RNA turnover viruses. Unexpected reactions were observed also with H-2d, H-2j and H-2r cells and absorption experiments indicated two or three antibody populations. These reactions could be interpreted by two different possibilities: (1) anti-H-2 antibodies react with virus-altered H-2 structures; and (2) anti-viral antibodies react with H-2 structures complexed with viruses. These possibilities should be taken into account when H-2 sera are tested on tumour or virus-infected cells.

Absorption↗
PubMed1979

Cross-reactivity among the products of three nonallelic H-2 loci, H-2Ld, H-2Dq, and H-2Kk.

Cross-reactions of the products of three nonallelic H-2 loci, H-2K, H-2D, and H-2L, have been studied by serological, immunochemical, and cellular immune techniques. Immunoprecipitation experiments revealed a determinant shared between Ld and Dq molecules but absent on Dd molecules, By cytotoxic screening of sera from individual mice an exceptional anti-Ld serum was found which cross-reacted with an H-2k antigen. Genetic mapping studies suggested that the basis of this activity was an Ld-Kk serological cross-reaction. Cytotoxic T cells generated to Ld alloantigens were also found to recognize a cross-reacting Kk determinant. These studies therefore suggest that L, D, and K are three structurally homologous cell surface glycoproteins that have evolved from a common primordial gene.

Animals↗