A novel HLA-DR beta I sequence from the DRw11 haplotype.
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Amino Acid Sequence↗
Biomedical subjects
M Schlesier
Publications and source records attributed to M Schlesier.
Autoreactive T cells in rheumatic disease. II. Function and specificity of an autoreactive T helper cell clone established from a HLA-B27+ reactive arthritis.
T cell lines were established by limiting dilution of peripheral blood (PBL) and synovial fluid lymphocytes (SFL) of a patient with HLA-B27+ reactive arthritis. Among these cell lines, the CD4 phenotype was dominant. Functionally, the majority of these cell lines exhibited helper activity for the immunoglobulin production by autologous B cells and proliferated in response to autologous mononuclear cells. In most cases, this autoreactive response was associated with alloreactivity. Only one cell line, the autoreactive CD4+ T cell clone, UA-S2, which was derived from the synovial fluid, proliferated in a highly specific manner in response to a determinant associated with MHC class II products present on autologous mononuclear cells. The restriction element was shown to be associated with DR molecules by inhibition experiments with monoclonal antibodies. Within the patient's family, the capacity of mononuclear cells to stimulate a proliferative response of UA-S2 segregated together with the HLA haplotype A2 or 32, B27, Cw1, DRw11 which was contributed by the patient's mother. UA-S2 proved to be a functional helper T cell clone. In the absence of additional antigen or mitogen, it induced IgG and IgM synthesis of autologous and family members' B cells. This helper activity of UA-S2 showed the same MHC restriction as the proliferative response. Although the patient's father also typed DRw11, this haplotype was not recognized by UA-S2. It is suggested that this autoreactive T cell clone detects a microheterogeneity of the serologically defined DRw11 haplotype. Indeed, typing of the patient's family members with cellular reagents established a difference between the two DRw11 haplotypes.
Arthritis, Rheumatoid↗
A novel serine proteinase (HuTSP) isolated from a cloned human CD8+ cytolytic T cell line is expressed and secreted by activated CD4+ and CD8+ lymphocytes.
A novel proteinase, termed human T cell-associated serine proteinase (HuTSP), has been highly purified from a human CD8+ T lymphocyte clone. By using a panel of chromogenic model peptide substrates the enzyme was found to specifically recognize L-arginine and to cleave Tos-Gly-Pro-Arg-nitroanilide with high efficiency at a pH optimum of 10.5-11. Exposure to class-specific proteinase inhibitors revealed that HuTSP is a serine endopeptidase. The enzyme has a mol. mass of approximately 50 kDa (non-reduced) and of approximately 25-30 kDa (reduced) when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis suggesting HuTSP to be a disulfide-linked dimer. The enzyme is shown to be inducible by lectin in both CD4+ and CD8+ lymphocytes. Moreover, HuTSP was detected in a number of independent CD4+ and CD8+ T cell clones and was found to be released from effector cells upon ligand binding to the CD3-T cell receptor complex.
Clone Cells↗
Quantitative absorption of interleukin-2 by peripheral blood and synovial fluid lymphocytes from patients with rheumatoid arthritis.
Peripheral blood (PBL) and synovial fluid lymphocytes (SFL) from 18 patients with definite rheumatoid arthritis (RA) and from one patient with Reiter's disease (RD) were examined for their capacity to absorb quantitatively interleukin-2 (IL-2) from a standardized, lectin-free IL-2 source. For comparison normal ConA blasts and PBL from various inflammatory and noninflammatory diseases as well as from healthy control persons were studied. IL-2 activity was quantitated by measuring 3H-thymidine-2-deoxyriboside uptake in the IL-2 dependent murine T cell line CTL6. ConA blasts exhibited a high IL-2 absorption capacity and served as a positive control for calibrating the absorption assay. In a population of normal PBL at least 5-10% of ConA blasts were required to detect IL-2 absorption. Significant absorption was assumed if more than 50% of IL-2 activity was removed from 200 microliters of a lectin-free IL-2 standard following incubation with 5 X 10(6) lymphoid cells for 2 h at 4 degrees C; this criterion was fulfilled with 8 out of 20 SFL and 4 out of 14 PBL preparations from RA patients. As a rule SFL absorbed more IL-2 than PBL. Control PBL did not absorb significant quantities of IL-2. PBL from the RD patient apparently produced an IL-2 inhibitor during incubation with the IL-2 standard. IL-2 absorption by ConA blasts and SFL was fully inhibited by preincubation of the absorbing cells with monoclonal anti-TAC antibody, a reagent known to react with the human IL-2 receptor. The results are discussed in view of current concepts of antigen/mitogen induced T cell activation.
Adult↗
Analysis of T-cell cultures and clones from a patient with classic rheumatoid arthritis--evidence for the existence of autoreactive T-cell clones in blood and synovial fluid.
Using lectin-free IL-2 as the only initial stimulus, bulk cultures and T-cell clones were established from synovial fluid (SFL) and peripheral blood lymphocytes (PBL) of a patient with rheumatoid arthritis (RA). The cloning efficiency of growing bulk cultures was 3%-4% as evaluated by Poisson statistics and was not enhanced by the addition of autologous synovial fluid or serum. The majority of the cloned T cells expressed the OKT8+ phenotype; several clones were OKT4+ and one clone expressed OKT8+ and OKT4+ antigens. None of the cloned T cells exhibited high NK or lectin-dependent cytotoxicity, although bulk cultures had high NK activity. In primed lymphocyte typing responses, bulk cultures and two T-cell clones established from rheumatoid SFL and PBL showed consistent autoreactivity, which we have never before observed with MLC-derived bulk cultures and T cell clones. One of the autoreactive rheumatoid T-cell clones (B25) was found to provide strong helper activity to autologous B cells in the absence of mitogen. Attempts to reveal reactivity of RA-derived T-cell clones to microbial antigens have so far only been successful with Mycoplasma pneumoniae preparations. Careful analysis of this reactivity revealed, however, that Mycoplasma pneumoniae induces a stimulator cell-dependent mitogenic effect rather than an antigen-specific MHC-restricted T-cell proliferation.
Antigens, Bacterial↗
[Terminal B-cell maturation and immunoglobulin synthesis in vitro in primary and secondary immune deficiencies].
Peripheral blood lymphocytes (PBL) from patients with various forms of primary and secondary immunodeficiencies and from 30 healthy control persons were examined for their capacity to show terminal B-cell maturation and immunoglobulin (Ig) synthesis in vitro following pokeweed mitogen (PWM) stimulation. PBL were cultured for 9 days with or without PWM and the percentages of B-cells or plasma cells with strongly positive cytoplasmic Ig (CIg+) were determined by indirect immunofluorescence on methanol fixed cytocentrifuged lymphocyte smears. In addition, newly synthesized IgA, IgG and IgM was measured in the cell free culture supernatant by means of a sensitive microplate ELISA. In 29 out of 30 control cultures the proportion of CIg+-cells increased markedly following 9-day stimulation with PWM. CIg+-cells and newly synthesized Ig were significantly correlated. In a group of 18 patients with common variable immunodeficiency (CVID) maturation to CIg+-cells was greatly impaired and the in vitro production of IgA and IgG was reduced. Two infants with severe combined immunodeficiency (SCID) failed to produce Ig prior to and following haplo-identical bone marrow transplantation despite the presence of immature B-cells. A heterogeneous group of secondary immunodeficiencies showed different forms of an impaired terminal B-cell maturation and a reduced capacity to synthesize Ig in vitro. The described PWM culture techniques in combination with the evaluation of CIg+-cells and the measurement of newly synthesized Ig in the culture supernatant proved to be a reliable in vitro correlate for terminal B-cell maturation and represent an important tool for the classification of humoral immunodeficiencies.
Adolescent↗
In vivo inactivation of soluble hydrogenase of Alcaligenes eutrophus.
The soluble, NAD+-reducing hydrogenase in intact cells of Alcaligenes eutrophus was inactivated by oxygen when electron donors such as hydrogen or pyruvate were available. The sole presence of either oxygen or oxidizable substrates did not lead to inactivation of the enzyme. Inactivation occurred similarly under autotrophic growth conditions with hydrogen, oxygen and carbon dioxide. The inactivation followed first order reaction kinetics, and the half-life of the enzyme in cells exposed to a gas atmosphere of hydrogen and oxygen (8:2, v/v) at 30 degrees C was 1.5h. The process of inactivation did not require ATP-synthesis. There was no experimental evidence that the inactivation is a reversible process catalyzed by a regulatory protein. The possibility is discussed that the inactivation is due to superoxide radical anions (O2-) produced by the hydrogenase itself.
Adenosine Triphosphate↗