Project: Research project

Grant Details


Monocytes play a central role in the induction of immune responses,
because of their capacity to generate signals required for T cell
activation. CD14 is a 52 kD glycoprotein primarily expressed on mature
monocytes. The function of CD14 is poorly understood. We have recently
shown that monoclonal antibodies (mAb) to human CD14 induce a marked
increase in monocyte adhesiveness. We have also strong evidence to
suggest that CD14 is involved in adhesion between activated T cells and
monocytes, and that engagement of CD14 results in inhibition of T cell
proliferation. Taken together, these findings suggest that CD14 plays a
regulatory role in monocyte-T cell interactions, which is mediated by
binding of CD14 to a putative natural ligand expressed on activated T
cells. We wish to study the role of CD14 in the human immune response. We
propose to: I. Study the role of CD14 in the regulation of T cell activation,
by assessing: (i) the mechanisms by which anti-CD14 mAb inhibit T cell
proliferation; (ii) the CD14 epitopes responsible for inhibition, and
(iii) heterogeneity of T cell sensitivity to inhibition via CD14. II. Clone the ligand for CD14 expressed on activated T cells. CD14-
mediated adhesion systems will be established and used to enrich and
screen a cDNA library obtained from activated human T cells. DNA probes
and mAbs specific for the CD14 ligand will be generated. Expression
cloning will be our first choice strategy; however, alternative
approaches will also be considered. III. Characterize the ligand for CD14, using specific mAbs and DNA
probes developed in the studies described in section II. We will study:
(i) the biochemical characteristics; (ii) the cellular distribution;
(iii) the induction of expression, and (iv) the role of the CD14 ligand
on T cells. The elucidation of the interactions between CD14 and its ligand will
result in a better understanding of monocyte-dependent regulation of T
cell responses, and will lead to the development of novel strategies to
interrupt T cell activation in disease states.
Effective start/end date7/16/915/31/96


  • National Institutes of Health: $105,083.00


  • Medicine(all)


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