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N A Mitchison

Publications and source records attributed to N A Mitchison.

At least 19 recordsLinked to original sources
PubMed1992

Specialization, tolerance, memory, competition, latency, and strife among T cells.

Over the last four decades much insight has been gained into the working of T cells. This survey offers an interpretation of regulatory T-cell function in terms of epitope linkage and the need to free B cells of responsibility for self-tolerance. These functions dictate specialized forms of antigen presentation, by separate populations of dendritic cells. Tolerance induction among T cells occurs at a threshold of antigen concentration which is close to that required for positive stimulation, as would be expected for the efficient working of the immune system. Certain self-proteins, especially those located on cell surfaces, also induce tolerance among B cells, thus reducing the danger of activating latent epitopes. Memory among T cells is attributed to two components, one of hyperreactivity of activated cells, and the other of clonal expansion. Examples of competition and buffering between T-cell activities are given. A brief discussion of autoimmune disease focusses on the importance of disease remission, protective HLA genes, and immunoinhibitory genes in animal models. The mechanism underlying all three may be a balance between competing subsets of T cells.

Autoimmunity↗
PubMed1991

Screening gene expression libraries for epitopes recognized in Mycobacterium leprae by mouse T cells.

Parasite expression libraries have so far been screened with antibodies, DNA probes or T cell clones. Immunity to many parasites, such as Mycobacterium leprae, is largely mediated by T cells, and so the screening of such libraries for T cell epitopes is an important step toward the development of effective vaccines and diagnostic reagents. A new method for screening of lambda gt11 libraries with uncloned T cell populations is presented here, which takes advantage of the fact that the recombinant proteins contain beta-galactosidase as their leader peptide; this allows them to be semipurified by means of anti-beta-galactosidase antibodies coated on the bottom of microtiter plate wells, within which a proliferation assay can then be carried out. Optimum conditions for the assay were determined, using the M. leprae 18-kDa antigen as a test antigen.

Animals↗
PubMed1991

A survey of biotechnology.

This issue on immunology and biotechnology opens with a survey of the contribution of immunology to medicine. Proteins, growth and differentiation factors, and monoclonal antibodies to surface antigens will have an impact in the 1990's likely similar to that of antibiotics in the 1950's. The characterization of factors and cell-surface molecules opens the investigation of the role of "recessive oncogenes" in the development of cancer. A further impact of immunology in the classical field of prophilaxis is represented by the innovative development of contraceptive vaccines based on the use of episomal shuttle vectors for the expression of surface sperm proteins able to induce an effective immune response.

Antibodies, Monoclonal↗
PubMed1990

An exact comparison between the efficiency of two- and three-cell-type clusters in mediating helper activity.

Adoptive transfer of anti-H-2Db-primed B cells combined with anti-minor histocompatibility antigen-primed T cells enables the effect of linked and unlinked alloantigen to be compared. Over an extensive dose range the unlinked antigen proved ineffective. In a previously described, exactly comparable system for assessing the same effect on cytotoxic T cell precursors, low doses of linked antigen had proved approximately equally effective, but high doses of unlinked antigen had proved effective. This contrast supports the hypothesis that whereas T-B collaboration is mediated by two-cell-type clusters, collaboration between T cells requires formation of three-cell-type clusters.

Animals↗
PubMed1990

Thy-1-specific helper T cells can provide intramolecular help, but can provide intermolecular help only if the phosphatidylinositol anchor of Thy-1 is replaced by a membrane insert.

We have investigated the ability of Thy-1 to serve as a helper antigen in delivering intermolecular help. The parental Thy-1 molecule, which is attached to the cell surface via a phosphatidylinositol anchor, failed to deliver intermolecular help for an antibody response to H-2 alloantigens. This failure appears to be due to the phosphatidylinositol anchor since a Thy-1 hybrid construct, which is expressed as a transmembrane cell surface molecule, can serve as helper antigen and deliver intermolecular help.

Animals↗
PubMed1990

Dominant reduced responsiveness controlled by H-2(Kb)Ab. A new pattern evoked by Thy-1 antigen and F liver antigen.

In the most frequently used panel of H-2 recombinant strains, B10.A, B10.A(4R), B10.A(5R), and B10, inhibition of the immune response has hitherto mapped to H-2E. Inhibition of the responses to Thy-1 antigen and to F liver protein, as described here, maps in a novel pattern to H-2KbAb, and presumably to H-2Ab. Enhancement of the adoptively transferred anti-Thy-1 response by treatment with CD8-specific antibody suggests, very provisionally, that T cells with suppressive activity mediate the inhibition. The evolution of this new pattern, and of dominant reduced responsiveness in general, is discussed and its relevance to immunological diseases assessed. An enzyme-linked immunosorbent assay (ELISA) for F-specific antibodies is introduced.

Animals↗
PubMed1990

The evolution of acquired immunity to parasites.

Evolutionary pressures exerted by parasites on the immune system, and vice versa, are surveyed from a speculative viewpoint. New information is presented about the possible channelling of suppression by MHC Class II genes in the mouse, where a novel pattern of dominant unresponsiveness mediated by H-2Ab is described. In addition, the hypothesis is advanced that phosphatidyl-inositol anchorage on the surface of parasites may represent a novel evasion mechanism, in which the spread of the immune response by epitope linkage is inhibited by host phospholipase.

Animals↗
PubMed1990

Purification of recombinant Mycobacterium leprae 65-kilodalton antigen and murine antibody responses to intravenously administered recombinant protein.

Recombinant Mycobacterium leprae 65-kilodalton antigen has been purified by a combination of differential solubility, ion-exchange and hydrophobic interaction chromatography, and a method for the quantification of the antigen in large scale protein preparations developed. By injecting large amounts of the recombinant antigen intravenously into mice, a limited degree of specific suppression of antibody-response has been induced.

Animals↗
PubMed1989

T cells in transplantation immunity.

This paper reviews the following problems in transplantation immunity: (i) short-lived ability to transfer immunity or suppression, in contrast to long-lived immunological memory in the autochthonous animal; (ii) short-lived ability to transfer graft-resistance, in contrast to long-lived ability to transfer helper activity for B-cells; (iii) the response to H-Y, as a system that might solve some outstanding problems in antigen presentation; and (iv) the contrast between live and killed allogeneic cells as immunogens. All of these problems, it is suggested, are amenable to study by modern methods. Students like me were drawn into Peter Medawar's orbit in the 1940s and 1950s by an irresistible mix of intellectual challenge and the glamour of experimental surgery. Much the same was happening elsewhere in the laboratories of Ray Owen, Milan Hasek, George Snell, Burnet, and Florey, and by 1960 the transplantation immunologists could justly claim to have opened up a whole new area of ideas in biology: we had discovered the lymphocyte as the antigen-sensitive cell, and the principles of immunological tolerance; we had revived interest in cellular immunity, and it was we who found the MHC (even if we had little idea of its real meaning). But by 1960 the first wave of success had passed, and the penetration of immunology by molecular biology had begun. Interest in transplantation immunity perceptibly declined, although many groups continued to address important problems, particularly in the field of organ transplantation. (ABSTRACT TRUNCATED AT 250 WORDS)

Graft Rejection↗
PubMed1989

Suppression.

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Animals↗
PubMed1989

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↗
PubMed1989

Problems in the physiology of class I and class II MHC molecules, and of CD45.

1. Co-processing of alloantigens suggests that epitope-loaded MHC class I molecules may pass from tissue cells to dendritic cells. 2. Antigen-presenting cells in the thymus need some special trick in order to load their MHC class II molecules with epitopes from "intermediate concentration" self-proteins in order to induce self-tolerance in developing cells. 3. Cell-cell interactions may transmit signals simply by rearranging surface glycoproteins and thus locally perturbing a phosphorylation equilibrium. 4. The CD45 and STB1 phenotype of most cells in the thymus may be characteristic of a doomed cell.

Animals↗
PubMed1989

Suppression of the response to murine alloantigens: four-cell-type clusters, function-flipping and idiosyncratic responses.

Specific immune suppression develops under certain well-defined conditions of exposure to antigen, where it is evident as a diminution of the immune response due to the activity of antigen-specific suppressor cells, usually T cells. Although subject to intensive study over the last two decades, interest in suppression has declined recently because of failure to make progress in defining molecular mechanisms or the precise cells involved. This review outlines present information, and then goes on to present three new ideas that emerge from study of murine alloantigens: (1) how the formation of four-cell-type clusters might mediate suppression; (2) a classification of means whereby class II MHC molecules may mediate suppression that includes a suggestion to account for the anomalous behaviour of H-2Ab; and (3) the value of idiosyncratic responses as probes of suppressor mechanisms. It does not provide an exhaustive coverage review of the literature, but recommends certain other reviews that do so.

Animals↗