PubMed HealthSearch

PubMed · 57073

beta2-Microglobulin: a reevaluation.

Abstract

Rabbit antiserum to human beta2-microglobulin was used to inhibit the proliferative response of lymphocytes in a variety of in vitro assays and to block the effector phase of the cell mediated lympholysis reaction. The antiserum was able to inhibit both of these reactions; it is not clear whether the cytotoxic reaction that we are studying in a xenogeneic human-rabbit system is based on phytohemagglutinin dependent cytotoxicity or on specific recognition of target cells by receptors on the effector cells, or most likely on a combination of both cytotoxic mechanisms. Whereas the possibility that beta2-microglobulin may be associated with receptors on the thymus-derived lymphocyte surface is considered, it is also pointed out that the effect of the antiserum may be based on other mechanisms of perturbing the membrane so as to inhibit these responses.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

M L Bach, K F Lindahl, M D Poulik. 1976. beta2-Microglobulin: a reevaluation.. https://pubmed.ncbi.nlm.nih.gov/57073/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Ligand-dependent conformational changes in the progesterone receptor are necessary for events that follow DNA binding.

Hormones and antihormones induce related, but distinct, conformational changes in the progesterone receptor [Allan, G. F., Leng, X., Tsai, S. Y., Weigel, N. L., Edwards, D. P., Tsai, M.-J. & O'Malley, B. W. (1992) J. Biol. Chem. 267, 19513-19520]. In both cases the conformational change precedes the dissociation of heat shock proteins and binding to DNA. We have now investigated the steps in hormone action which are dependent upon this conformational change. We show that in the absence of ligand, monoclonal antibodies directed against different regions of the progesterone receptor can induce high-affinity binding to its response element in vitro. This antibody-induced DNA binding is presumably facilitated by enhanced dimerization of receptor monomers. However, antibodies do not induce the hormone-specific conformational change in the progesterone receptor and do not induce in vitro transcription by the receptor. In contrast, the antiprogestin ZK98299, which inhibits receptor binding to DNA, fully induces the antihormone-specific conformational change. Thus, our data imply that steroids induce a conformational change in their receptors which is necessary for events subsequent to DNA binding, most likely for transactivation.

Antigen-Antibody Reactions

Studies of the 'hook' effect in the one-step sandwich immunoassay.

The one-step sandwich immunoassay is increasingly replacing the traditional two-step immunoassay due to obvious advantages such as assay speed. However, the one-step sandwich immunoassay suffers from the 'hook' effect irrespective of the analyte characteristics. The 'hook' effect is dependent primarily on the analyte concentration. Three different model analytes, human growth hormone (hGH), the dimeric form of hGH (D-hGH, having a discrete number of repeating epitopes) and ferritin (multiple epitopes) having different immunological properties have been employed in studies of the one-step sandwich immunoassay. The characteristics of each of the model analytes offer new insights into general guidelines for assay procedures. These guidelines permit rapid optimization of assay conditions for an immunoassay without a priori knowledge of the immunological characteristics of the antibody or antigen. Both experimental and theoretical data show several instances where high capacity solid-phase antibodies can effectively shift the 'hook' to relatively higher analyte concentrations. The effect of the concentration of labeled antibody on assay response was examined theoretically.

Antigen-Antibody Reactions

Kinetics of anti-CD4-induced T helper cell depletion and inhibition of function. Activation of T cells by the CD3 pathway inhibits anti-CD4-mediated T cell elimination and down-regulation of cell surface CD4.

In vivo treatment with anti-CD4 antibody profoundly suppresses a number of T cell-dependent responses and is clinically useful in the treatment of certain mouse models of autoimmune disease. Treatment with anti-CD4 antibody will inactivate and can deplete CD4 T cells, but the mechanisms responsible for these effects are incompletely understood. When mouse spleen cells were exposed in vitro to both SRBC and monoclonal anti-CD4, there was 55% reduction of the anti-SRBC response. If cultures were preincubated with anti-CD4 for 48 h before in vitro challenge, the reduction was greater than 80%. When unfractionated spleen cells were cultured with anti-CD4 for 96 h, there was actual elimination of CD4 cells in these cultures since virtually all CD3+ cells were CD8+. Activation of T cells by exposure to anti-CD3 rendered them resistant to antibody-mediated CD4 depletion. This resistance to CD4 depletion was seen even in cultures that were pretreated with anti-CD4 for as long as 24 h before anti-CD3 exposure. In cultures of purified T cells, anti-CD4 did not eliminate CD4 T cells. However, culture of T cells with macrophage-rich adherent cells and anti-CD4 resulted in elimination of CD4 T cells. Thus, it appears that macrophages play a role in anti-CD4-induced T cell elimination. While anti-CD4 did not eliminate CD4 cells from a population of purified T cells, there was profound down-regulation of cell surface CD4. Activating T cells with immobilized anti-CD3 before addition of anti-CD4 prevented down-regulation of CD4. These experiments demonstrate that T cell activation by anti-CD3 renders the activated cells resistant to antibody-induced CD4 down-regulation and to antibody-induced CD4 T cell depletion. These findings may have relevance to the application of anti-CD4 therapy in human diseases that are mediated by activated Th cells.

Antigen-Antibody Reactions