Methodology, Limitations and Uses of Antigen-binding Assays in the Analysis of T Cell Receptor-Antigen Interactions

1988 ◽  
pp. 113-132
Author(s):  
B. E. Elliott ◽  
R. G. E. Palfree ◽  
S. Mundinger ◽  
Z. A. Nagy
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Antigen Binding ◽  
Binding Assays

scholarly journals A framework for highly multiplexed dextramer mapping and prediction of T cell receptor sequences to antigen specificity

2021 ◽  
Vol 7 (20) ◽  
pp. eabf5835
Author(s):  
Wen Zhang ◽  
Peter G. Hawkins ◽  
Jing He ◽  
Namita T. Gupta ◽  
Jinrui Liu ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Adaptive Immune System ◽  
Cell Receptor ◽  
Immune Monitoring ◽  
Binding Assays ◽  
Antigen Specificity ◽  
Interaction Map ◽  
Antigen Interaction ◽  
Context Specific

T cell receptor (TCR) antigen–specific recognition is essential for the adaptive immune system. However, building a TCR-antigen interaction map has been challenging due to the staggering diversity of TCRs and antigens. Accordingly, highly multiplexed dextramer-TCR binding assays have been recently developed, but the utility of the ensuing large datasets is limited by the lack of robust computational methods for normalization and interpretation. Here, we present a computational framework comprising a novel method, ICON (Integrative COntext-specific Normalization), for identifying reliable TCR-pMHC (peptide–major histocompatibility complex) interactions and a neural network–based classifier TCRAI that outperforms other state-of-the-art methods for TCR-antigen specificity prediction. We further demonstrated that by combining ICON and TCRAI, we are able to discover novel subgroups of TCRs that bind to a given pMHC via different mechanisms. Our framework facilitates the identification and understanding of TCR-antigen–specific interactions for basic immunological research and clinical immune monitoring.

scholarly journals Amino acid substitutions in the floor of the putative antigen-binding site of H-2T22 affect recognition by a gamma delta T-cell receptor

1993 ◽  
Vol 90 (23) ◽  
pp. 11396-11400 ◽  
Author(s):  
S Moriwaki ◽  
B S Korn ◽  
Y Ichikawa ◽  
L van Kaer ◽  
S Tonegawa
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Peptide Transporter ◽  
Affect Recognition ◽  
Antigen Binding ◽  
In Vitro Mutagenesis ◽  
Gamma Delta ◽  
T Cell Clone ◽  
Gamma Delta T Cell

We have previously identified a self-reactive gamma delta T-cell clone (KN6) specific for the H-2T region gene product T22b. Now we have investigated by an in vitro mutagenesis analysis of the T22b gene the possibility that the interaction between the KN6 gamma delta T-cell receptor and T22b involves a peptide. The results demonstrate that mutations at the floor of the putative antigen-binding groove of T22b affect recognition by the gamma delta T-cell receptor. Furthermore, we have shown that KN6 cells react with cells that are deficient in the class I peptide transporter TAP1/TAP2. These results suggest that peptide is involved in the interaction of the KN6 T-cell receptor with T22 and that loading of T22 with the putative peptide is TAP1/TAP2-independent.

scholarly journals Stoichiometry of the murine γδ T cell receptor

2006 ◽  
Vol 203 (1) ◽  
pp. 47-52 ◽  
Author(s):  
Sandra M. Hayes ◽  
Paul E. Love
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Subunit Composition ◽  
Invariant Chain ◽  
Antigen Binding ◽  
Γδ T Cell ◽  
Cell Lineages ◽  
Receptor Complexes ◽  
Γδ T Cell Receptor

The T cell receptor for antigen (TCR) complex is organized into two functional domains: the antigen-binding clonotypic heterodimer and the signal-transducing invariant CD3 and TCRζ chains. In most vertebrates, there are two different clonotypic heterodimers (TCRαβ and TCRγδ) that define the αβ and γδ T cell lineages, respectively. αβ- and γδTCRs also differ in their invariant chain subunit composition, in that αβTCRs contain CD3γε and CD3δε dimers, whereas γδTCRs contain only CD3γε dimers. This difference in subunit composition of the αβ- and γδTCRs raises the question of whether the stoichiometries of these receptor complexes are different. As the stoichiometry of the murine γδTCR has not been previously investigated, we used two quantitative immunofluorescent approaches to determine the valency of TCRγδ heterodimers and CD3γε dimers in surface murine γδTCR complexes. Our results support a model of murine γδTCR stoichiometry in which there are two CD3γε dimers for every TCRγδ heterodimer.

Deep learning-based prediction of the T cell receptor–antigen binding specificity

2021 ◽  
Author(s):  
Tianshi Lu ◽  
Ze Zhang ◽  
James Zhu ◽  
Yunguan Wang ◽  
Peixin Jiang ◽  
...  
Keyword(s):  
Deep Learning ◽  
T Cell ◽  
T Cell Receptor ◽  
Binding Specificity ◽  
Cell Receptor ◽  
Antigen Binding

scholarly journals Functional analysis of the antigen binding site on the T cell receptor alpha chain.

1992 ◽  
Vol 175 (6) ◽  
pp. 1553-1563 ◽  
Author(s):  
E A Nalefski ◽  
S Kasibhatla ◽  
A Rao
Keyword(s):  
Amino Acid ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Antigen Recognition ◽  
Single Amino Acid ◽  
Antigen Binding ◽  
Amino Acid Substitutions ◽  
Wild Type ◽  
Alpha Chain

We have identified residues on a T cell receptor (TCR) alpha chain that are important for interaction with antigen/major histocompatibility complex (MHC). Using site-directed mutagenesis, we modified DNA encoding the postulated antigen/MHC binding loops on the TCR alpha chain expressed by the T cell clone D5, which recognizes p-azobenzenearsonate-conjugated antigens presented by cells bearing I-Ad. These variant TCR alpha chains were expressed in conjunction with the wild-type D5 TCR beta chain on the surface of hybridoma cells, and were tested for the ability to recognize hapten-conjugated antigens presented by I-Ad. Individual amino acid substitutions in each of the three antigen binding loops (alpha 1, alpha 2, alpha 3) of the D5 TCR alpha chain affected antigen recognition, demonstrating that all three loops are important in recognition of antigen/MHC. A subset of the single amino acid substitutions completely eliminated antigen recognition, thus identifying the residues that are particularly important in the recognition of antigenic peptide/MHC by the D5 TCR. Because the wild-type D5 TCR recognizes arsonate and certain structural analogues of arsonate conjugated to a variety of protein antigens, we were able to test whether the TCR substitutions affected the specificity of the D5 TCR for hapten or carrier antigen. One substitution introduced into antigen binding loop alpha 3 markedly altered the pattern of carrier recognition. Together, these results verify the Ig model for the TCR and are consistent with the proposition that residues forming the first and second antigen binding loops of the TCR contact the MHC, while those forming the third loop contact mainly antigenic peptides.

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