Receptor on the surface of activated T-cells: ACT-4

Abstract

The invention provides purified ACT-4 receptor polypeptides, antibodies against these polypeptides and nucleic acids encoding ACT-4 receptor polypeptides. Also provided are methods of diagnosis and treatment using the same. ACT-4 receptors are preferentially expressed on the surface of activated CD4+ T-cells. ACT-4 receptors are usually expressed at low levels on the surface of activated CD8+ cells, and are usually substantially absent on resting T-cells, and on monocytes and B-cells (resting or activated). An exemplary ACT-4 receptor, termed ACT-4-h-1, has a signal sequence, an extracellular domain comprising three disulfide-bonded intrachain loops, a transmembrane domain, and an intracellular domain.

Description

TECHNICAL FIELD [0001] This invention relates generally to the isolation and characterization of a cell-surface receptor, termed ACT-4, and antibodies thereto, and the use of the antigen and antibodies for monitoring and / or modulating immune responses. BACKGROUND OF THE INVENTION [0002] Immune responses are largely mediated by a diverse collection of peripheral blood cells termed leukocytes. The leukocytes include lymphocytes, granulocytes and monocytes. Granulocytes are further subdivided into neutrophils, eosinophils and basophils. Lymphocytes are further subdivided into T and B lymphocytes. T-lymphocytes originate from lymphocytic-committed stem cells of the embryo. Differentiation occurs in the thymus and proceeds through prothymocyte, cortical thymocyte and medullary thymocyte intermediate stages, to produce various types of mature T-cells. These subtypes include CD8+ T cells (also known as cytotoxic / suppressor T cells), which, when activated, have the capacity to lyse target c...

AI Technical Summary

Benefits of technology

[0015] In another aspect, the invention provides methods of suppressing an immune response in a patient suffering from an immune disease or condition. A therapeutically effective dose of a pharmaceutical c

Problems solved by technology

However, undesired immune response can occur following transplantation of foreign tissue, or in an autoimmune disease, in which one of a body's own antigens is the target for the immune response.

Agents, particularly antibodies, that block receptors of immune cells from binding to soluble molecules or cell-bound receptors can impair immune responses.

Although some trials have shown encouraging results, significant problems remain.

First, a patient may develop an immune response toward the blocking agent preventing continued immunosuppressive effects unless different agents are available.

In this situation, continued treatment with a single immunosuppressive agent is ineffective.

Third, many targets for therapeutic agents are located on more than one leukocyte subtype, with the result that it is generally not possible to selectively block or eliminate the response of only specific cellular subtypes and thereby leave unimpaired a residual immune capacity for combating infectious microorganisms.

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