The Enigmatic Nature of the TCR-pMHC Interaction: Implications for CAR-T and TCR-T Engineering
The interaction of the T-cell receptor (TCR) with a peptide in the major histocompatibility complex (pMHC) plays a central role in the adaptive immunity of higher chordates. Due to the high specificity and sensitivity of this process, the immune system quickly recognizes and efficiently responds to...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/23/14728 |
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| author | D. V. Shevyrev V. P. Tereshchenko S. V. Sennikov |
| author_facet | D. V. Shevyrev V. P. Tereshchenko S. V. Sennikov |
| author_sort | D. V. Shevyrev |
| collection | DOAJ |
| description | The interaction of the T-cell receptor (TCR) with a peptide in the major histocompatibility complex (pMHC) plays a central role in the adaptive immunity of higher chordates. Due to the high specificity and sensitivity of this process, the immune system quickly recognizes and efficiently responds to the appearance of foreign and altered self-antigens. This is important for ensuring anti-infectious and antitumor immunity, in addition to maintaining self-tolerance. The most common parameter used for assessing the specificity of TCR-pMHC interaction is affinity. This thermodynamic characteristic is widely used not only in various theoretical aspects, but also in practice, for example, in the engineering of various T-cell products with a chimeric (CAR-T) or artificial (TCR-engineered T-cell) antigen receptor. However, increasing data reveal the fact that, in addition to the thermodynamic component, the specificity of antigen recognition is based on the kinetics and mechanics of the process, having even greater influence on the selectivity of the process and T lymphocyte activation than affinity. Therefore, the kinetic and mechanical aspects of antigen recognition should be taken into account when designing artificial antigen receptors, especially those that recognize antigens in the MHC complex. This review describes the current understanding of the nature of the TCR-pMHC interaction, in addition to the thermodynamic, kinetic, and mechanical principles underlying the specificity and high sensitivity of this interaction. |
| first_indexed | 2024-03-09T17:46:59Z |
| format | Article |
| id | doaj.art-f248717d7391405da4bc4896d5f63822 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T17:46:59Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f248717d7391405da4bc4896d5f638222023-11-24T11:06:55ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123231472810.3390/ijms232314728The Enigmatic Nature of the TCR-pMHC Interaction: Implications for CAR-T and TCR-T EngineeringD. V. Shevyrev0V. P. Tereshchenko1S. V. Sennikov2Laboratory of molecular Immunology, Research Institute for Fundamental and Clinical Immunology, 630099 Novosibirsk, RussiaLaboratory of molecular Immunology, Research Institute for Fundamental and Clinical Immunology, 630099 Novosibirsk, RussiaLaboratory of molecular Immunology, Research Institute for Fundamental and Clinical Immunology, 630099 Novosibirsk, RussiaThe interaction of the T-cell receptor (TCR) with a peptide in the major histocompatibility complex (pMHC) plays a central role in the adaptive immunity of higher chordates. Due to the high specificity and sensitivity of this process, the immune system quickly recognizes and efficiently responds to the appearance of foreign and altered self-antigens. This is important for ensuring anti-infectious and antitumor immunity, in addition to maintaining self-tolerance. The most common parameter used for assessing the specificity of TCR-pMHC interaction is affinity. This thermodynamic characteristic is widely used not only in various theoretical aspects, but also in practice, for example, in the engineering of various T-cell products with a chimeric (CAR-T) or artificial (TCR-engineered T-cell) antigen receptor. However, increasing data reveal the fact that, in addition to the thermodynamic component, the specificity of antigen recognition is based on the kinetics and mechanics of the process, having even greater influence on the selectivity of the process and T lymphocyte activation than affinity. Therefore, the kinetic and mechanical aspects of antigen recognition should be taken into account when designing artificial antigen receptors, especially those that recognize antigens in the MHC complex. This review describes the current understanding of the nature of the TCR-pMHC interaction, in addition to the thermodynamic, kinetic, and mechanical principles underlying the specificity and high sensitivity of this interaction.https://www.mdpi.com/1422-0067/23/23/14728TCRmechanosensorpMHCaffinityCAR-TTCR-engineering |
| spellingShingle | D. V. Shevyrev V. P. Tereshchenko S. V. Sennikov The Enigmatic Nature of the TCR-pMHC Interaction: Implications for CAR-T and TCR-T Engineering International Journal of Molecular Sciences TCR mechanosensor pMHC affinity CAR-T TCR-engineering |
| title | The Enigmatic Nature of the TCR-pMHC Interaction: Implications for CAR-T and TCR-T Engineering |
| title_full | The Enigmatic Nature of the TCR-pMHC Interaction: Implications for CAR-T and TCR-T Engineering |
| title_fullStr | The Enigmatic Nature of the TCR-pMHC Interaction: Implications for CAR-T and TCR-T Engineering |
| title_full_unstemmed | The Enigmatic Nature of the TCR-pMHC Interaction: Implications for CAR-T and TCR-T Engineering |
| title_short | The Enigmatic Nature of the TCR-pMHC Interaction: Implications for CAR-T and TCR-T Engineering |
| title_sort | enigmatic nature of the tcr pmhc interaction implications for car t and tcr t engineering |
| topic | TCR mechanosensor pMHC affinity CAR-T TCR-engineering |
| url | https://www.mdpi.com/1422-0067/23/23/14728 |
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