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Molecular mechanism and function of CD40/CD40L engagement in the immune system

Authors


Randolph J. Noelle
Department of Microbiology and Immunology
Dartmouth Medical School and The Norris Cotton Cancer Center
1 Medical Center Drive
Rubin Bldg, Level 7, Room 730
Lebanon, NH 03756, USA
Tel.: +1 603 653 9918
Fax: +1 603 653 9952
e-mail: Randolph.J.Noelle@Dartmouth.edu

Abstract

Summary:  During the generation of a successful adaptive immune response, multiple molecular signals are required. A primary signal is the binding of cognate antigen to an antigen receptor expressed by T and B lymphocytes. Multiple secondary signals involve the engagement of costimulatory molecules expressed by T and B lymphocytes with their respective ligands. Because of its essential role in immunity, one of the best characterized of the costimulatory molecules is the receptor CD40. This receptor, a member of the tumor necrosis factor receptor family, is expressed by B cells, professional antigen-presenting cells, as well as non-immune cells and tumors. CD40 binds its ligand CD40L, which is transiently expressed on T cells and other non-immune cells under inflammatory conditions. A wide spectrum of molecular and cellular processes is regulated by CD40 engagement including the initiation and progression of cellular and humoral adaptive immunity. In this review, we describe the downstream signaling pathways initiated by CD40 and overview how CD40 engagement or antagonism modulates humoral and cellular immunity. Lastly, we discuss the role of CD40 as a target in harnessing anti-tumor immunity. This review underscores the essential role CD40 plays in adaptive immunity.

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