Autologous cell therapy depends on T lymphocyte expansion efficiency and is hindered by suboptimal interactions between T cell receptors (TCR) and peptide‐MHC molecules. Various artificial antigen presenting cell systems that enhance these interactions are often labor‐intensive, fabrication costly, highly variable, and potentially unscalable toward clinical setting. Here, 3D centrifugation‐enabled priming of T cell immune‐synapse junctions is performed to generate tight T cell–Dynabead aggregates at a rate 200‐fold faster than that of conventional 24‐h bulk shaking. Furthermore, by forming T cell–Dynabead aggregates in the starting culture, two‐ to sixfold greater T cell expansion is achieved over conventional T cell expansion for cancer patient‐derived primary T cells while limiting over‐activation. Creating 3D T cell–Dynabead aggregates as the “booster” material enables highly efficient polyclonal T cell expansion without the need for complex surface modification of artificial antigen‐presenting cells (APCs). This method can be modularly adapted to existing T cell expansion processes for various applications, including adoptive cell therapies (ACTs).
αβ and γδ T cell receptors (TCRs) are highly diverse antigen receptors that define two evolutionarily conserved T cell lineages. We describe a population of γμTCRs found exclusively in non-eutherian mammals that consist of a two-domain (Vγ-Cγ) γ-chain paired to a three-domain (Vμ-Vμj-Cμ) μ-chain. γμTCRs were characterized by restricted diversity in the Vγ and Vμj domains and a highly diverse unpaired Vμ domain. Crystal structures of two distinct γμTCRs revealed the structural basis of the association of the γμTCR heterodimer. The Vμ domain shared the characteristics of a single-domain antibody within which the hypervariable CDR3μ loop suggests a major antigen recognition determinant. We define here the molecular basis underpinning the assembly of a third TCR lineage, the γμTCR.
more » « less- NSF-PAR ID:
- 10218864
- Publisher / Repository:
- American Association for the Advancement of Science (AAAS)
- Date Published:
- Journal Name:
- Science
- Volume:
- 371
- Issue:
- 6536
- ISSN:
- 0036-8075
- Page Range / eLocation ID:
- p. 1383-1388
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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