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E J Ball

Publications and source records attributed to E J Ball.

36 records · Page 2Linked to original sources
PubMed1986

Recognition of class II molecules by human T cells. I. Analysis of epitopes of DR and DQ molecules in a DRw11, DRw52, DQw3 haplotype.

The HLA-D region of individuals with the DRw11, w52, DQw3 haplotype encodes multiple molecular products of three distinct subregions, DR, DP, and DQ. Since each molecule can carry multiple stimulatory epitopes, the repertoire of allogeneic T-cell responses to determinants of this haplotype can be quite large. In the present experiments, alloreactive cloned T-cell lines recognized six distinct epitopes associated with DRw11, DRw52, DQw3 haplotypes. Panel studies established that three epitopes were DRw11-like and three were DRw52-like. Blocking with monoclonal antibodies showed that two DRw11-like epitopes were carried by DR-subregion products and one DRw11-like epitope was carried by DQ-subregion molecules. DRw52-like epitopes were detected on separate DR subregion-encoded molecules. One of them carried both DRw11- and DRw52-like epitopes, the other carried two of the DRw52-like epitopes. These epitopes, which represent functional units that trigger T-cell responses, can be detected at the present time only with the methods used in this report. Conventional allogeneic T-cell responses represent the summation of responses to multiple epitopes encoded by different D-subregion genes.

Antibodies, Monoclonal↗
PubMed1986

Human alveolar macrophages: HLA-DR-positive macrophages that are poor stimulators of a primary mixed leukocyte reaction.

Previous studies demonstrated that alveolar macrophages (AM) from most normal human volunteers failed to stimulate the antigen-induced proliferation of peripheral blood T lymphocytes although greater than 90% of AM expressed HLA-DR antigens. The current studies establish that AM also fail to induce allogeneic peripheral blood mononuclear cells to proliferate in a mixed leukocyte reaction (MLR). Suppressive activity by AM was not an explanation for their failure to induce an MLR. Indirect immunofluorescence established the presence of both HLA-DR and DQ antigens on the majority of AM and the persistence of these antigens on cells in culture for up to 6 days, the period of time required to observe a maximal MLR. Metabolic labeling experiments also demonstrated that HLA-DR antigens were synthesized by AM. It was recently reported that AM secrete relatively small amounts of IL 1, an important ancillary signal provided by accessory cells to enhance the stimulation of lymphocyte proliferation. However, addition of optimal concentrations of IL 1 to cultures containing AM failed to enhance the MLR. Thus, there is at least one additional, but as yet undefined, requirement for an accessory cell to induce an optimal MLR besides the display of HLA-D region antigens and the secretion of IL 1. In contrast, AM were effective in specifically stimulating proliferation of alloreactive T cell lines, suggesting that at least some cell lines do not require this nonspecific undefined second signal. We speculate that although AM may not initiate primary immune responses in the lung, they may be important in maintaining immune-mediated inflammatory responses by specifically restimulating already activated T cells.

Adult↗
PubMed1985

Bronchoalveolar cells from sarcoid patients demonstrate enhanced antigen presentation.

The recognition of foreign antigens by T lymphocytes in association with lung antigen-presenting cells may be critical in the initiation of the mononuclear alveolitis and granuloma formation of pulmonary sarcoidosis. However, it has been shown that bronchoalveolar cells (BAC) from normal volunteers function poorly as antigen-presenting cells. Therefore, the ability of sarcoid BAC to serve as accessory cells for antigen-dependent autologous T cell proliferation, as measured by tritiated thymidine uptake, was compared with that of normal BAC. Although irradiated sarcoid BAC supported antigen-induced T cell proliferation, normal BAC did so poorly (p less than 0.005). Because it has been shown that sarcoid BAC produce more interleukin 1 (IL 1) than normal BAC, it was considered that the enhancement of antigen-induced proliferative responses could result from an increased amount of IL 1, and that contaminating monocytes in the peripheral blood T cell preparations displayed the antigen for T cell recognition. Therefore, it was necessary to establish that antigen-induced T cell responses required HLA-D region compatibility between the sarcoid BAC and T lymphocytes. BAC from sarcoid patients stimulated antigen-specific proliferation in T cells lines matched for at least one HLA-D-region antigen, but failed to stimulate T cell lines that were unmatched for both antigens. This finding indicates that cells in bronchoalveolar lavage fluids from sarcoid patients were fully capable of acting as antigen-presenting cells. The identification of antigen-presenting cells in the lungs of patients with sarcoidosis together with the previous findings of activated T cells, enhanced IL 1 production, and spontaneous interleukin 2 release in sarcoid patients is compatible with the hypothesis that local cell-mediated immunity is involved in the pathogenesis of pulmonary sarcoidosis.

Adult↗
PubMed1984

Antigen-specific HLA-restricted human T-cell lines. II. A GAT-specific T-cell line restricted by a determinant carried by an HLA-DQ molecule.

Human T-cell lines responsive to the polypeptide antigens GAT and (T,G)-A--L were developed. They were specific for the priming antigens and required the participation of accessory cells matched for HLA-linked determinants, as shown in family studies. In panel studies, the ability of accessory cells to present antigen was shown to be associated with HLA-D-region antigens. However, the specificity of these determinants did not fully correspond to any HLA antigens as currently defined. One GAT-specific subline, derived by limiting dilution, utilized a restriction determinant associated with, but distinct from, the DQw3 (MB3) allospecificity. Blocking studies with mouse monoclonal antibodies indicated that this restriction determinant was carried by HLA-DQ molecules. The epitopes recognized in these molecules appear to be distinct from the alloantigenic determinants currently defined by serology.

Antibodies, Monoclonal↗
PubMed1984

Antigen-specific HLA-restricted human T-cell lines. I. An MT3-like restriction determinant distinct from HLA-DR.

The results presented provide evidence that the HLA specificity known as MT3, BR4, or Hon7 can serve as a restriction epitope for the proliferation of certain T cells responding to mumps viral antigen. This restriction determinant was found to be HLA-linked in family studies, and to segregate centromeric to a crossover between HLA-B and DR in one family. In the population studied, the specificity was found to be associated with the DR antigens DR4, DR7, and DRw9, which are known to be associated with MT3. The ability of accessory cells to present mumps antigen in the context of this supertypic restriction determinant was blocked by a monoclonal antibody specific for MT3. Since MT3 (BR4, Hon7) has been shown to be expressed on molecules distinct from DR, our experiments suggest that such molecules are functionally important in antigen presentation to T cells.

Antibodies, Monoclonal↗
PubMed1984

Different specificities of an HLA-DRw6 haplotype detected by alloreactive T lymphocytes.

DRw6 has been difficult to define serologically. In the present experiments we have developed T cell lines in order to characterize the components of a DRw6 haplotype. This was accomplished by priming T cells with allogeneic mononuclear cells mismatched for DRw6, Dw6, and MT2. Subsequently, three sublines with distinct reactivity patterns were derived by limiting dilution. The specificities detected by these sublines included: (a) a specificity found on a subset of cells positive for DRw6 which was inhibited by monoclonal antibodies against DS(DC), the human homologue of the murine IA-encoded molecules, (b) another DRw6-associated specificity blocked by an MT2-like antibody, and (c) an MT2-like specificity blocked by monoclonal antibodies reactive with a different MT2-associated determinant. These results show that more than one IE-like, as well as the DS/DC (IA-like) molecules, carry distinctive antigenic epitopes that can be recognized by allogeneic T cells. Primed T cell lines may be useful for a better definition of certain haplotypes which are at present difficult to characterize with serological reagents alone.

Antibodies, Monoclonal↗
PubMed1984

The use of cellular reagents as an adjunct to typing for HLA-DRw10.

Two human T cell lines recognizing DRw10 were generated. One line was directly alloreactive, while a second cloned line recognized mumps virus in the context of a DRw10-like determinant. In panel studies, the lines responded only to DRw10 cells, and not to DR1 (DRw10-) cells. When compared to 5 anti-DRw10 sera, the cellular reagents gave virtually identical results. The generation and use of such cellular reagents may be of particular value for the identification of HLA-D-region specificities that are rare, poorly defined, or for which serologic typing reagents are limited.

Cell Line↗
PubMed1984

Expression of HLA-DR, MB, MT and SB antigens on human mononuclear cells: identification of two phenotypically distinct monocyte populations.

The expression of HLA-DR, SB, MB, and MT antigens in different populations of human mononuclear cells was investigated with the use of monoclonal antibodies that recognize distinct human Ia-like antigens. Our results indicate that in man, as previously reported in other species, two phenotypically distinct populations of monocytes or macrophages can be identified on the basis of expression of Class II MHC antigens. Virtually all circulating monocytes displayed determinants associated with HLA-DR, SB, and MT. In addition, a subpopulation of human monocytes expressed MB/DS-associated antigens, as detected with monoclonal antibodies specific for MB1, MB3, and DS-framework determinants. Most B lymphocytes expressed antigens associated with HLA-DR, and the specificities SB2, SB3, MB1, MB3, MT2, and MT3 were also present. Resting T lymphocytes were unreactive with antibodies that recognize all of the Class II MHC antigens tested. T lymphocytes activated by soluble antigen or alloantigens, and expanded in culture, expressed DR, SB, MB, and MT. The majority of the MB/DS+ cells present in the adherent population were monocytes, because they were phagocytic and had the monocyte-specific marker 63D3. The rest of the cells were not identified. They are likely to include mostly B lymphocytes. The presence of other cells, such as dendritic cells, in this subset needs to be determined.

Antibodies, Monoclonal↗
PubMed1983

Accessory cell function of human endothelial cells. I. A subpopulation of Ia positive cells is required for antigen presentation.

The expression of class I and class II HLA antigens on preparations of human endothelial cells, isolated from umbilical cord veins, was investigated by immunofluorescence. While virtually all endothelial cells expressed class I antigens, less than 1% were positive for class II antigens, as detected with a panel of 10 different monoclonal antibodies. Antigen specific T cell lines proliferated in response to mumps antigen in the presence of endothelial cells or blood monocytes from HLA-DR matched donors. However, these T cell lines failed to respond in the absence of accessory cells or when accessory cells from HLA-D-region mismatched cord donors were used. The ability of both monocytes and endothelial cells to present antigen was abolished by treatment of the cells with monoclonal antibodies specific for either class I or class II HLA antigens plus complement. Similar treatment with monoclonal antibodies specific for monocytes greatly reduced antigen presentation by endothelial cells. These results indicate that preparations of endothelial cells contain a subpopulation of Ia positive cells, distinct from monocytes, which are required for antigen presentation.

Animals↗
PubMed1982

Cell-mediated cytotoxicity against HLA-D-region products expressed in monocytes and B lymphocytes. IV. Characterization of effector cells using monoclonal antibodies against human T-cell subsets.

The cytotoxic effector cells that recognize HLA-D-region determinants and their precursors were characterized using monoclonal antibodies against human T lymphocytes and T-cell subsets. These studies were performed using MLC combinations giving rise to cytotoxic cells specific for both class I (HLA-A, B, C) and class II (HLA-D-region) antigens, and then tested against target cells displaying relevant antigens of only one class. Both class I and class II specific CTL (cytotoxic T lymphocytes) were inhibited by treatment with the OKT3 monoclonal antibody and complement, indicating that the effector cells were T lymphocytes. A major portion of class II specific CTL, and their precursors, were inhibited by OKT4 and complement, while class I specific CTL from the same cultures were not. The T4+T8- cell subset has previously been associated with helper or inducer functions, but not with cytotoxicity. The present findings indicate that class I and class II specific CTL, and their precursors, are different on the basis of the class of target antigen recognized and on the basis of surface phenotype detected by monoclonal antibodies.

Antibodies, Monoclonal↗
PubMed1982

Development of protective immunity against bacterial and viral infections in tumor-bearing mice coincident with suppression of tumor immunity.

This report addresses the question whether Meth A (methylcholanthrene-induced fibrosarcoma) tumor bearing Balb/c mice are able to develop specific antimicrobial immunity. Although specific suppressor T lymphocytes appeared during tumor growth which prevented expression of antitumor immunity, the development of protective immunity to L monocytogenes, S. pneumoniae or ectromelia virus infections was unimpaired. The Meth A tumor produced a soluble immunosuppressive factor which inhibited lymphocyte and macrophage functions in vitro. Tumor growth failed to inhibit the formation of immunoglobulin essential to antipneumococcal immunity, or the development of a specific acquired cellular resistance of primary importance in immunity to listeria and ectromelia virus infections. That tumor growth did not interfere with the development of cell mediated immunity was demonstrated by the effective transfer of antilisteria immunity by immune spleen from tumor-bearing mice.

Animals↗
PubMed1981

Cell mediated cytotoxicity against HLA-D region products expressed in monocytes and B lymphocytes. III. Inhibition by monoclonal antibodies and study of an HLA-B/DR recombinant.

Attempts to further define the antigens recognized by HLA-D-region specific cytotoxic lymphocytes were undertaken using monocytes and transformed B cell lines as target cells. Monoclonal antibody against framework determinants of HLA-DR antigens partially blocked cell mediated lysis, suggesting that at least a portion of the D-region specific cytotoxic cells recognized the HLA-DR determinants. The study of a family with an HLA-B/DR recombinant showed that the determinants recognized by allogeneic anti-HLA-D-region cytotoxic lymphocytes are encoded outside of HLA-B. In addition, cytotoxic lymphocytes specific for the HLA-D region could be generated with cells identical throughout the interval from HLA-A to B and disparate only to the left of HLA-B.

Antibodies, Monoclonal↗
PubMedDate not supplied

The use of body mass index to predict body composition in children.

BACKGROUND: Simple anthropometric indices of body composition have particular appeal for use in children, and as such body mass index (BMI) has been used to predict percentage body fat in a number of studies. AIM: To evaluate the relationship between BMI and percentage body fat (%body fat) and a proposed, more appropriate relationship between BMI and fat mass/height(2) in a cohort of young children. SUBJECTS AND METHODS: Cross-sectional study of 109 children aged between 6 and 10 years residing in either Sydney or Brisbane, Australia. Weight and height were measured using standard methods. Body composition was measured using a stable isotope method to firstly determine total body water and subsequently fat free mass. RESULTS: The correlation between BMI and fat mass/height(2) was markedly greater than that between BMI and percentage body fat. In the entire group of children the R(2) (x100%) value for the relationship between BMI and fat mass/height(2) was 73.3% compared with 46.5% for the relationship between BMI and percentage body fat. CONCLUSIONS: We have shown that the use of BMI to predict fat mass/height(2), and consequently percentage body fat, is superior to the use of BMI to predict percentage body fat based directly upon the R(2) values of the above analysis.

Anthropometry↗