The CD28-Transmembrane Domain Mediates Chimeric Antigen Receptor Heterodimerization With CD28.

Details

Serval ID
serval:BIB_35407AE1906E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The CD28-Transmembrane Domain Mediates Chimeric Antigen Receptor Heterodimerization With CD28.
Journal
Frontiers in immunology
Author(s)
Muller Y.D., Nguyen D.P., Ferreira LMR, Ho P., Raffin C., Valencia RVB, Congrave-Wilson Z., Roth T.L., Eyquem J., Van Gool F., Marson A., Perez L., Wells J.A., Bluestone J.A., Tang Q.
ISSN
1664-3224 (Electronic)
ISSN-L
1664-3224
Publication state
Published
Issued date
2021
Peer-reviewed
Oui
Volume
12
Pages
639818
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Anti-CD19 chimeric antigen receptor (CD19-CAR)-engineered T cells are approved therapeutics for malignancies. The impact of the hinge domain (HD) and the transmembrane domain (TMD) between the extracellular antigen-targeting CARs and the intracellular signaling modalities of CARs has not been systemically studied. In this study, a series of 19-CARs differing only by their HD (CD8, CD28, or IgG <sub>4</sub> ) and TMD (CD8 or CD28) was generated. CARs containing a CD28-TMD, but not a CD8-TMD, formed heterodimers with the endogenous CD28 in human T cells, as shown by co-immunoprecipitation and CAR-dependent proliferation of anti-CD28 stimulation. This dimerization was dependent on polar amino acids in the CD28-TMD and was more efficient with CARs containing CD28 or CD8 HD than IgG <sub>4</sub> -HD. The CD28-CAR heterodimers did not respond to CD80 and CD86 stimulation but had a significantly reduced CD28 cell-surface expression. These data unveiled a fundamental difference between CD28-TMD and CD8-TMD and indicated that CD28-TMD can modulate CAR T-cell activities by engaging endogenous partners.
Keywords
CAR, CAR T cell, CD28, chimeric antigen receptor, dimer, heterodimerization, hinge domain, transmembrane domain
Pubmed
Web of science
Open Access
Yes
Create date
12/04/2021 13:20
Last modification date
17/04/2021 6:33
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