Cancer of the cervix: prospects for immunological control.
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Female↗
Biomedical subjects
B M Chain
Publications and source records attributed to B M Chain.
Further studies on the regulation of lymphokine biosynthesis in contact sensitivity.
Contact sensitivity (CS) results from a series of cellular interactions involving CD4+ T cells and macrophages. We have studied the production of lymphokines by T cells from mice immunized by contact sensitization and by a variety of stimuli leading to CS or tolerance to CS. Primed T cells from mice immunized for CS are predominantly of the TH1 type. Conversely, a failure in the activation of these antigen-specific TH1 cells is a key step in the induction of tolerance to CS. Spleen cells from tolerant mice can suppress the production of lymphokines from primed cells, both in an adoptive transfer system and when mixed with effector cells in vitro. The relative importance of lymphokine competition, prostaglandin production by adherent cells, and other mechanisms underlying this suppression is discussed.
Animals↗
Definition of murine T helper cell determinants in the major capsid protein of human papillomavirus type 16.
Three murine major histocompatibility complex (MHC) class II-restricted T cell determinants were identified in the major capsid protein L1 of human papillomavirus (HPV) type 16. Peptides derived from HPV-16 L1, which contain putative T cell epitopes located by a predictive algorithm, were synthesized and tested for lymphoproliferative activity by direct immunization, followed by in vitro assay of responses to peptides or recombinant HPV-16 L1. The MHC restriction of the stimulatory peptides was determined using blocking monoclonal antibodies against class II molecules. The responses, which were specific for the priming peptides alone, cross-reacted with recombinant L1 but not with analogous peptides derived from other HPV types.
Amino Acid Sequence↗
Antigen processing: current issues, exceptional cases (Thy 1 alloantigen, MHC class-II-restricted cytolytic T cells), and implications for vaccine development.
A dogmatic view of antigen processing is presented in outline, followed by a survey of unresolved issues in the subject. The activity of Thy 1 as an alloantigen, and allospecific MHC Class-II-restricted cytolytic T cells offer examples of exceptional cases of antigen presentation. Implications for the design of vaccines are drawn.
Animals↗
A cell-free model system for the study of antigen processing.
Antigen processing is an essential step in the presentation of most protein antigens to class 2 MHC restricted T cells, but many of the details of processing remain unknown. In this study we show that a whole cell lysate, as well as membrane fractions from an antigen-presenting B cell lymphoma, can process ovalbumin. In this system native ovalbumin incubated with these membranes at acidic pH can be presented to an antigen-specific hybridoma by gluteraldehyde-fixed, antigen-presenting cells. This processing is inhibited by pepstatin, a selective inhibitor of aspartyl proteases. This is the first study of processing by subcellular fractions, and this cell-free system will provide a good model in which to dissect further the molecular requirements of antigen processing.
Animals↗
The T-cell response to haptenated insulins. I. The proliferative response.
Mice were primed with TNP-derivatized insulin, or TNP-Mycobacteria, and lymph node cells were challenged in vitro with haptenated and unhaptenated antigens. Using either priming antigen, T-cell proliferative responses could be obtained to TNP-insulin. In B10 (H-2b), mice, which are responders to beef insulin (BI), but not to pork insulin (PI), TNP-BI or TNP-PI primed a response to TNP beef and TNP pork insulins, and to beef but not pork insulin, suggesting that a proportion of the response was directed to the modified portion of the molecule. However, priming with BI resulted in responsiveness to TNP-PI, but not to PI. Also, TNP-BI stimulated an augmented proliferative response in BI-primed mice. These results suggest that TNP modification can alter the antigenicity of the carrier molecule, perhaps by enhancing weak interactions with MHC molecules on presenting cells. Finally, there was no evidence that the TNP-dependent response to TNP-pork insulin was down-regulated by suppressor cells directed at the carrier molecule.
Animals↗
The T-cell response to haptenated insulins. II. The antibody response.
As described in an accompanying paper, trinitrophenyl (TNP) modification of pork insulin (PI) at the A1 glycine position allows this molecule to stimulate a proliferative response in H-2b (B10) mice. We now show that this antigen stimulates low IgG responses in the same strain of mice. Our results show that T-cell help and proliferation may therefore be regulated independently.
Adoptive Transfer↗
Endopeptidase activities associated with the plasma membrane compartment of an antigen-presenting B cell.
Endopeptidase activity was characterized in plasma membranes prepared from an antigen-presenting B cell lymphoma, A20. Activity was detected at both neutral and acid pH, and studies with inhibitors confirmed that a number of different enzymes, most probably cysteine, metallo, and aspartic endopeptidases, were associated with the A20 cell surface.
Animals↗
The stimulation of IL-2 production by anti-rheumatic drugs.
IL-2 release from mouse splenocytes was measured by assaying the IL-2 on an IL-2-dependent cytotoxic T-lymphocyte line in culture (CTLL). Proliferation of the CTLL cells was monitored indirectly with the dye thiazolyl blue. The slow-acting anti-rheumatic drug auranofin at concentrations below 0.1 microM potentiated concanavalin A (Con A)-induced IL-2 release. Similar potentiation of Con A-induced IL-2 release was obtained with D-penicillamine, 1 microM-1 mM, and with the angiotensin-converting enzyme-inhibitor captopril, 10 nM-1 microM. Potentiation of Con A-induced IL-2 release was obtained with concentrations of the drugs likely to be achieved in vivo during therapy. Auranofin but not D-penicillamine and captopril inhibited Con A-induced IL-2 release at high concentrations (greater than 0.3 microM).
Animals↗
Chromatographic analysis of the trinitrophenyl derivatives of insulin.
The insulin molecule was derivatised by reaction with trinitrobenzenesulphonic acid (TNBS), which is known to react predominantly with free primary amino groups. The products of the reaction were analysed by reversed-phase chromatography and by further derivatisation with dansyl chloride. Under the conditions of these experiments, TNBS was found to react preferentially with glycine at position A1. This finding is discussed in terms of the tertiary structure and immunogenicity of this derivative.
Chromatography, High Pressure Liquid↗
The biochemistry and cell biology of antigen processing.
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Animals↗
The cellular pathway of antigen presentation: biochemical and functional analysis of antigen processing in dendritic cells and macrophages.
The response of primed T cells to keyhole limpet haemocyanin (KLH) was used to compare the characteristics of antigen presentation by lymphoid dendritic cells, splenic and peritoneal macrophages. In a similar manner to macrophages, purified dendritic cells could be pulsed with antigen and subsequently fixed by brief glutaraldehyde fixation and still retain antigen presenting activity. Also, as previously reported for macrophages, presentation could be inhibited by chloroquine. These functional experiments suggested that the pathway of antigen presentation in dendritic cells and macrophages was similar or identical. However, biochemical studies, using radiolabelled antigen, showed that dendritic cells do not significantly degrade large proteins such as KLH to TCA-soluble form, but partially hydrolyse them to smaller peptide fragments. The significance of these results in terms of a model of the cellular pathways of antigen presentation is discussed.
Animals↗
Presentation by peritoneal macrophages: modulation by antibody-antigen complexes.
The effects of immune complex formation on presentation was studied. Immune complexes between an IgG2a monoclonal anti-DNP antibody and TNP-KLH were produced, and the presentation of the carrier molecule by peritoneal macrophages to KLH-primed T cells was monitored. Complex formation was found to enhance the proliferative response of the T cells. This enhancement was specific, was not mediated by lymphokine release, and required antibody with an intact Fc portion. The significance of these results in terms of immune regulation and antigen presentation is discussed.
Animals↗
Nonphagocytic dendritic cells are effective accessory cells for anti-mycobacterial responses in vitro.
The accessory cell requirements for a given T cell response may be examined in vitro by using highly purified lymph node T cells. We have examined the capacity of different antigen-presenting cells to stimulate proliferation of Mycobacterium tuberculosis-primed T cells when the antigenic challenge is either soluble or particulate in nature. By titrations of cell number and antigen concentration, it was shown that dendritic cells are not only extremely efficient at presenting soluble mycobacterial antigen compared with various macrophage populations, but also that they are capable of presenting whole mycobacteria. Because phagocytosis of mycobacteria does not occur with these cells, we suggest that processing of antigen by dendritic cells may be initiated at the plasma membrane. Because macrophages are not essential for this in vitro response, a role for dendritic cells in antibacterial immunity in vivo is implicated.
Animals↗
Observations on the cytochemistry of the hemocytes of an insect, Galleria mellonella.
A number of cytochemical parameters of the hemocytes of larval Galleria mellonella, an insect frequently used as a model by comparative cellular immunologists, are described. Cytochemical methods were used to quantify hemocyte granule-associated components, the results are compared to those obtained for leukocytes from higher animals. Granulocytes contained a population of nonlysosomal granules rich in mucopolysaccharide not seen in plasmatocytes. The numbers and dimensions of these granules showed a positive correlation to cell size, probably reflecting a developmental sequence in granulocyte maturation. Both granulocytes and plasmatocytes had other granules containing the typical lysosomal enzymes, acid phosphatase, beta-glucuronidase, esterase, and lysozyme. The nonlysosomal enzyme alkaline phosphatase was not found in Galleria hemocytes; it is also absent from vertebrate monocytes, macrophages, and immature polymorphonuclear leukocytes. Insect hemocytes appear to lack certain components of antibacterial systems typical of mammalian blood cells, such as H2O2-generating systems, cationic proteins, and myeloperoxidase. The bactericidal mechanisms of hemocytes probably involve lysozyme, as well as other biologically active cellular and humoral factors unique to insects.
Animals↗
Does the T-cell receptor bind to the MHC?
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Histocompatibility Antigens↗