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Increased Peptide Contacts Govern High Affinity Binding of a Modified TCR Whilst Maintaining a Native pMHC Docking Mode

Overview of attention for article published in Frontiers in immunology, January 2013
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  • Good Attention Score compared to outputs of the same age (69th percentile)
  • Good Attention Score compared to outputs of the same age and source (75th percentile)

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Title
Increased Peptide Contacts Govern High Affinity Binding of a Modified TCR Whilst Maintaining a Native pMHC Docking Mode
Published in
Frontiers in immunology, January 2013
DOI 10.3389/fimmu.2013.00168
Pubmed ID
Authors

David K. Cole, Malkit Sami, Daniel R. Scott, Pierre J. Rizkallah, Oleg Y. Borbulevych, Penio T. Todorov, Ruth K. Moysey, Bent K. Jakobsen, Jonathan M. Boulter, Brian M. Baker, Yi Li

Abstract

Natural T cell receptors (TCRs) generally bind to their cognate pMHC molecules with weak affinity and fast kinetics, limiting their use as therapeutic agents. Using phage display, we have engineered a high affinity version of the A6 wild-type TCR (A6wt), specific for the human leukocyte antigen (HLA-A(∗)0201) complexed with human T cell lymphotropic virus type 111-19 peptide (A2-Tax). Mutations in just 4 residues in the CDR3β loop region of the A6wt TCR were selected that improved binding to A2-Tax by nearly 1000-fold. Biophysical measurements of this mutant TCR (A6c134) demonstrated that the enhanced binding was derived through favorable enthalpy and a slower off-rate. The structure of the free A6c134 TCR and the A6c134/A2-Tax complex revealed a native binding mode, similar to the A6wt/A2-Tax complex. However, concordant with the more favorable binding enthalpy, the A6c134 TCR made increased contacts with the Tax peptide compared with the A6wt/A2-Tax complex, demonstrating a peptide-focused mechanism for the enhanced affinity that directly involved the mutated residues in the A6c134 TCR CDR3β loop. This peptide-focused enhanced TCR binding may represent an important approach for developing antigen specific high affinity TCR reagents for use in T cell based therapies.

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The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 61 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 2 3%
Unknown 59 97%

Demographic breakdown

Readers by professional status Count As %
Researcher 14 23%
Student > Ph. D. Student 13 21%
Student > Bachelor 7 11%
Other 4 7%
Student > Doctoral Student 3 5%
Other 7 11%
Unknown 13 21%
Readers by discipline Count As %
Agricultural and Biological Sciences 18 30%
Biochemistry, Genetics and Molecular Biology 11 18%
Medicine and Dentistry 6 10%
Engineering 4 7%
Chemistry 4 7%
Other 6 10%
Unknown 12 20%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 20 April 2023.
All research outputs
#8,261,140
of 25,371,288 outputs
Outputs from Frontiers in immunology
#10,107
of 31,507 outputs
Outputs of similar age
#84,490
of 288,991 outputs
Outputs of similar age from Frontiers in immunology
#107
of 503 outputs
Altmetric has tracked 25,371,288 research outputs across all sources so far. This one has received more attention than most of these and is in the 66th percentile.
So far Altmetric has tracked 31,507 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.4. This one has gotten more attention than average, scoring higher than 66% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 288,991 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 69% of its contemporaries.
We're also able to compare this research output to 503 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 75% of its contemporaries.