2016
DOI: 10.1073/pnas.1518499113
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Functional evidence for TCR-intrinsic specificity for MHCII

Abstract: How T cells become restricted to binding antigenic peptides within class I or class II major histocompatibility complex molecules (pMHCI or pMHCII, respectively) via clonotypic T-cell receptors (TCRs) remains debated. During development, if TCR-pMHC interactions exceed an affinity threshold, a signal is generated that positively selects the thymocyte to become a mature CD4 + or CD8 + T cell that can recognize foreign peptides within MHCII or MHCI, respectively. But whether TCRs possess an intrinsic, subthresho… Show more

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Cited by 26 publications
(44 citation statements)
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“…When a CD3T subunit was expressed as a fusion with monomeric enhanced GFP (mEGFP), we used a GGGSAAAG linker. C-terminally truncated versions of CD4 (CD4T: aa1–421), with or without the Δbind mutation (aa:68–73 KGVLIR to DGDSDS), fused to mCherry via a AAAG linker were used in this study (26, 29). Glycine-based linkers were used for our fusion proteins because flexibility is required to allow equivalent probability of dipole alignment between FRET pairs, and even a single glycine in a dipeptide linker can allow a strand to double back upon itself (3034).…”
Section: Methodsmentioning
confidence: 99%
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“…When a CD3T subunit was expressed as a fusion with monomeric enhanced GFP (mEGFP), we used a GGGSAAAG linker. C-terminally truncated versions of CD4 (CD4T: aa1–421), with or without the Δbind mutation (aa:68–73 KGVLIR to DGDSDS), fused to mCherry via a AAAG linker were used in this study (26, 29). Glycine-based linkers were used for our fusion proteins because flexibility is required to allow equivalent probability of dipole alignment between FRET pairs, and even a single glycine in a dipeptide linker can allow a strand to double back upon itself (3034).…”
Section: Methodsmentioning
confidence: 99%
“…After washing, the beads were then probed with anti-TCRα (α–Vα11 RR8-1 APC eBioscience) and anti-CD3ε (145–2C11 PE BD) with fluorescently labeled mAbs. Analysis was then performed by flow cytometry to assess co-precipitation of TCRα, CD3ε, and CD3xT G (mEGFP) with TCRβ similarly to previously described protocols (29, 40, 41). …”
Section: Methodsmentioning
confidence: 99%
“…Such a potential study would lend insight into more conserved regions of TCRs and how different TCRs have devised unique strategies to interact with their ligands. The present study (7) provides further clues into how 500 million years of evolution has led to a recognition system that is paradoxically both specific and flexible. Although many questions linger and require additional investigation, whether the TCR has an inherent bias for MHC is becoming an answerable one.…”
mentioning
confidence: 78%
“…Despite years of work exploring reasons for this predisposition, a clear consensus remains elusive. In PNAS, Parrish et al, using a sensitive in vitro system, provide new evidence to suggest that TCRs possess an inherent bias to recognize MHC molecules (7).…”
mentioning
confidence: 99%
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