title: A transendocytosis perspective on the CD28/CTLA-4 pathway.
abstract: T cell activation is a key event in the adaptive immune response and vital to the generation of both cellular and humoral immunity. Activation is required not only for effective CD4 T cell responses but also to provide help for B cells and the generation of cytotoxic T cell responses. Unsurprisingly, impaired T cell activation results in infectious pathology, whereas dysregulated activation can result in autoimmunity. The decision to activate is therefore tightly regulated and the CD28/CTLA-4 pathway represents this apical decision point at the molecular level. In particular, CTLA-4 (CD152) is an essential checkpoint control for autoimmunity; however, the molecular mechanism(s) by which CTLA-4 achieves its regulatory function are not well understood, especially how it functionally intersects with the CD28 pathway. In this chapter, we review the established molecular and cellular concepts relating to CD28 and CTLA-4 biology, and attempt to integrate these by discussing the transendocytosis of ligands as a new model of CTLA-4 function.
authors.affiliation: School of Immunity and Infection, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Blagoje
authors.initials: B
authors.lastname: Soskic
authors.affiliation: Cellular Sciences, UCB, Berkshire, United Kingdom.
authors.forename: Omar S
authors.initials: OS
authors.lastname: Qureshi
authors.affiliation: UCL Institute of Immunity and Transplantation, Royal Free Campus, London, United Kingdom.
authors.forename: Tiezheng
authors.initials: T
authors.lastname: Hou
authors.affiliation: UCL Institute of Immunity and Transplantation, Royal Free Campus, London, United Kingdom. Electronic address: d.sansom@ucl.ac.uk.
authors.forename: David M
authors.initials: DM
authors.lastname: Sansom
mesh_terms: D000818:Animals; D015551:Autoimmunity; D018106:CD28 Antigens / Q000378:metabolism*; D060908:CTLA-4 Antigen / Q000378:metabolism*; D004705:Endocytosis / Q000276:immunology*; D006801:Humans; D056747:Immunomodulation; D008213:Lymphocyte Activation; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018106:CD28 Antigens; D060908:CTLA-4 Antigen
keywords: CD28; CD80; CD86; CTLA-4; Costimulation; Tolerance; Transendocytosis; Treg