T Cells Compete by Cleaving Cell Surface CD27 and Blocking Access to CD70-bearing APCs

Overview

Journal Eur J Immunol

Specialty Allergy & Immunology

Date 2015 Jul 17

PMID 26179759

Citations 14

Authors

Matthew A Burchill

Beth A Tamburini

Ross M Kedl

Affiliations

Soon will be listed here.

Abstract

T cells compete against each other for access to molecules on APCs in addition to peptide/MHC complexes. However, the identity of cell surface molecules that influence T-cell competition, other than peptide/MHC, have yet to be defined. Here, we identify CD70, a TNF ligand expressed on activated APCs, as an important mediator of T-cell competition for APCs. Upon engagement of CD27 by CD70, CD27 is proteolytically cleaved from the surface of the interacting CD8(+) T cell and captured by CD70 expressing dendritic cells. The capture of CD27 effectively masks CD70 on APCs, disallowing the interaction with CD27 on other competing T cells. Collectively, our data indicate that T cells compete against each other for access to the TNF-ligand CD70, an interaction that affects the duration and potency of T cell/DC interactions, thus influencing the repertoire of responding CD8(+) T cells to self or foreign antigens.

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References

Kuka M, Munitic I, Giardino Torchia M, Ashwell J . CD70 is downregulated by interaction with CD27. J Immunol. 2013; 191(5):2282-9. PMC: 3750068. DOI: 10.4049/jimmunol.1300868. View

He L, Prostak N, Thomas L, Vitale L, Weidlick J, Crocker A . Agonist anti-human CD27 monoclonal antibody induces T cell activation and tumor immunity in human CD27-transgenic mice. J Immunol. 2013; 191(8):4174-83. DOI: 10.4049/jimmunol.1300409. View

Kato K, Chu P, Takahashi S, Hamada H, Kipps T . Metalloprotease inhibitors block release of soluble CD27 and enhance the immune stimulatory activity of chronic lymphocytic leukemia cells. Exp Hematol. 2007; 35(3):434-42. DOI: 10.1016/j.exphem.2006.10.018. View

Vitale L, He L, Thomas L, Widger J, Weidlick J, Crocker A . Development of a human monoclonal antibody for potential therapy of CD27-expressing lymphoma and leukemia. Clin Cancer Res. 2012; 18(14):3812-21. DOI: 10.1158/1078-0432.CCR-11-3308. View

Sanchez P, McWilliams J, Haluszczak C, Yagita H, Kedl R . Combined TLR/CD40 stimulation mediates potent cellular immunity by regulating dendritic cell expression of CD70 in vivo. J Immunol. 2007; 178(3):1564-72. DOI: 10.4049/jimmunol.178.3.1564. View

Edwards L, Haluszczak C, Kedl R . Phenotype and function of protective, CD4-independent CD8 T cell memory. Immunol Res. 2012; 55(1-3):135-45. PMC: 3922058. DOI: 10.1007/s12026-012-8356-9. View

van Gisbergen K, Klarenbeek P, Kragten N, Unger P, Nieuwenhuis M, Wensveen F . The costimulatory molecule CD27 maintains clonally diverse CD8(+) T cell responses of low antigen affinity to protect against viral variants. Immunity. 2011; 35(1):97-108. DOI: 10.1016/j.immuni.2011.04.020. View

Zehn D, Lee S, Bevan M . Complete but curtailed T-cell response to very low-affinity antigen. Nature. 2009; 458(7235):211-4. PMC: 2735344. DOI: 10.1038/nature07657. View

Widney D, Gundapp G, Said J, van der Meijden M, Bonavida B, Demidem A . Aberrant expression of CD27 and soluble CD27 (sCD27) in HIV infection and in AIDS-associated lymphoma. Clin Immunol. 1999; 93(2):114-23. DOI: 10.1006/clim.1999.4782. View

10.

Loenen W, de Vries E, Gravestein L, Hintzen R, van Lier R, Borst J . The CD27 membrane receptor, a lymphocyte-specific member of the nerve growth factor receptor family, gives rise to a soluble form by protein processing that does not involve receptor endocytosis. Eur J Immunol. 1992; 22(2):447-55. DOI: 10.1002/eji.1830220224. View

11.

Kara I, Sahin B, Gunesacar R . Levels of serum and cerebrospinal fluid soluble CD27 in the diagnosis of leptomeningeal involvement of hematolymphoid malignancies. Adv Ther. 2007; 24(4):741-7. DOI: 10.1007/BF02849967. View

12.

Tamburini B, Burchill M, Kedl R . Antigen capture and archiving by lymphatic endothelial cells following vaccination or viral infection. Nat Commun. 2014; 5:3989. PMC: 4073648. DOI: 10.1038/ncomms4989. View

13.

Moon J, Chu H, Pepper M, McSorley S, Jameson S, Kedl R . Naive CD4(+) T cell frequency varies for different epitopes and predicts repertoire diversity and response magnitude. Immunity. 2007; 27(2):203-13. PMC: 2200089. DOI: 10.1016/j.immuni.2007.07.007. View

14.

Hendriks J, Xiao Y, Borst J . CD27 promotes survival of activated T cells and complements CD28 in generation and establishment of the effector T cell pool. J Exp Med. 2003; 198(9):1369-80. PMC: 2194245. DOI: 10.1084/jem.20030916. View

15.

Kedl R, Schaefer B, Kappler J, Marrack P . T cells down-modulate peptide-MHC complexes on APCs in vivo. Nat Immunol. 2001; 3(1):27-32. DOI: 10.1038/ni742. View

16.

Thomas L, He L, Marsh H, Keler T . Targeting human CD27 with an agonist antibody stimulates T-cell activation and antitumor immunity. Oncoimmunology. 2014; 3(1):e27255. PMC: 3937191. DOI: 10.4161/onci.27255. View

17.

Ahonen C, Doxsee C, McGurran S, Riter T, Wade W, Barth R . Combined TLR and CD40 triggering induces potent CD8+ T cell expansion with variable dependence on type I IFN. J Exp Med. 2004; 199(6):775-84. PMC: 2212721. DOI: 10.1084/jem.20031591. View

18.

Willis R, Kappler J, Marrack P . CD8 T cell competition for dendritic cells in vivo is an early event in activation. Proc Natl Acad Sci U S A. 2006; 103(32):12063-8. PMC: 1524925. DOI: 10.1073/pnas.0605130103. View

19.

Keller A, Xiao Y, Peperzak V, Naik S, Borst J . Costimulatory ligand CD70 allows induction of CD8+ T-cell immunity by immature dendritic cells in a vaccination setting. Blood. 2009; 113(21):5167-75. DOI: 10.1182/blood-2008-03-148007. View

20.

McHeyzer-Williams M, Davis M . Antigen-specific development of primary and memory T cells in vivo. Science. 1995; 268(5207):106-11. DOI: 10.1126/science.7535476. View