Unique features of the TCR repertoire of reactivated memory T cells in the experimental mouse tumor model

Kalinina, Anastasiia; Persiyantseva, Nadezda A.; Britanova, Olga V.; Lupyr, Ksenia R; Shagina, Irina; Хромых, Л. М.; Kazansky, Dmitry

doi:10.1016/j.csbj.2023.05.028

Cited by 2 publications

(6 citation statements)

References 51 publications

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“…Taking this into account, we expect that the identification of α-chain-centric TCRs of antigen-specific memory T cells with cross-reactivity to multiple antigens could be a promising strategy to improve the efficacy of ACT [55,58]. Notably, minor changes in the CDR physicochemical features of TCRβ memory clonotypes were revealed in our study, further confirming the hypothesis of the TCRα dominating role in tumor antigen recognition by memory T cells [55].…”

Section: Tcrα Can Dictate the Mode Of Tcr Interaction With Pmhcsupporting

confidence: 85%

Section: Tcrα Can Dictate the Mode Of Tcr Interaction With Pmhcmentioning

confidence: 99%

“…In light of this supposition, our recent bioinformatics study of TCRα/β physicochemical features in tumor antigen-specific memory T cells is of particular interest [55]. We exploited an experimental mouse tumor model to generate primary activated effectors and reactivated memory T cells specific to tumor antigens [55,56]. This experimental system allowed us to track sequential changes in features of TCRα/β clonotypes involved in the primary and secondary anti-tumor immune responses.…”

Section: Tcrα Can Dictate the Mode Of Tcr Interaction With Pmhcmentioning

confidence: 99%

“…Interestingly, Dolton et al described a T cell clone isolated from tumor-infiltrating lymphocytes (TILs) of the melanoma patient after successful TIL-therapy that expressed the TCR specific to three melanoma antigens [57]. Taking this into account, we expect that the identification of α-chain-centric TCRs of antigen-specific memory T cells with cross-reactivity to multiple antigens could be a promising strategy to improve the efficacy of ACT [55,58]. Notably, minor changes in the CDR physicochemical features of TCRβ memory clonotypes were revealed in our study, further confirming the hypothesis of the TCRα dominating role in tumor antigen recognition by memory T cells [55].…”

Section: Tcrα Can Dictate the Mode Of Tcr Interaction With Pmhcmentioning

confidence: 99%

“…Our recent work showed that the CDR3 region of the TCRα clonotypes of tumorspecific memory T cells clearly differed from the CDR3α of primarily activated effector clonotypes in its physicochemical features and was enriched with hydrophobic, strongly interacting, and bulky amino acids [55]. Hence, in combination with other bioinformatics strategies, the analysis of TCRα/β physicochemical characteristics could be a reliable approach to defining clonotypes in the patient's bulk TCR repertoire, which are involved in anti-tumor responses.…”

Section: Identification Of Tumor-specific Tcrsmentioning

confidence: 99%

See 4 more Smart Citations

T Cell Receptor Chain Centricity: The Phenomenon and Potential Applications in Cancer Immunotherapy

Kalinina,

Khromykh,

Kazansky

2023

IJMS

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T cells are crucial players in adaptive anti-cancer immunity. The gene modification of T cells with tumor antigen-specific T cell receptors (TCRs) was a milestone in personalized cancer immunotherapy. TCR is a heterodimer (either α/β or γ/δ) able to recognize a peptide antigen in a complex with self-MHC molecules. Although traditional concepts assume that an α- and β-chain contribute equally to antigen recognition, mounting data reveal that certain receptors possess chain centricity, i.e., one hemi-chain TCR dominates antigen recognition and dictates its specificity. Chain-centric TCRs are currently poorly understood in terms of their origin and the functional T cell subsets that express them. In addition, the ratio of α- and β-chain-centric TCRs, as well as the exact proportion of chain-centric TCRs in the native repertoire, is generally still unknown today. In this review, we provide a retrospective analysis of studies that evidence chain-centric TCRs, propose patterns of their generation, and discuss the potential applications of such receptors in T cell gene modification for adoptive cancer immunotherapy.

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Section: Tcrα Can Dictate the Mode Of Tcr Interaction With Pmhcsupporting

confidence: 85%

Section: Tcrα Can Dictate the Mode Of Tcr Interaction With Pmhcmentioning

confidence: 99%

Section: Tcrα Can Dictate the Mode Of Tcr Interaction With Pmhcmentioning

confidence: 99%

Section: Tcrα Can Dictate the Mode Of Tcr Interaction With Pmhcmentioning

confidence: 99%

Section: Identification Of Tumor-specific Tcrsmentioning

confidence: 99%

See 3 more Smart Citations

T Cell Receptor Chain Centricity: The Phenomenon and Potential Applications in Cancer Immunotherapy

Kalinina,

Khromykh,

Kazansky

2023

IJMS

Self Cite

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T-cell receptor chain centricity in the primarily activated effectors and re-stimulated memory cells

Kalinina,

Kubekina,

Persiyantseva

et al. 2024

BRSMU

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T cells, the adaptive immunity effectors, carry an antigen-recognizing T-cell receptor (TCR) that represents an αβ heterodimer. Functional dominance of one chain has been reported for a number of TCRs. This feature is called chain centricity. Today, it is unclear whether chain centricity is an inherent feature of some TCRs, and what mechanism underlies its development. The study aimed to determine the abundance of such receptors in the repertoire of primarily activated effectors and re-stimulated memory cells of mice specific to the allogeneic tumor antigens. The long-lived memory cells formed in the primary immune response in vivo were in vitro re-stimulated with the immunizing tumor cells. Primary effectors were obtained in vitro in the culture by stimulation of T cells of non-immunized mice with cells of the same allogeneic tumor. TCR libraries of effectors involved in the primary and secondary immune response were created by NGS sequencing. To identify chain-centric TCRs, 10 ТCRα variants were selected from each repertoire. T cells of intact mice were modified with individual TCR α-chain variants by transduction, with subsequent assessment of T cell proliferation under exposure to specific allogeneic stimulators. In vitro screening revealed 10% of chain-centric receptors in the primary effector pool, and the proportion of such TCRs in the repertoire of re-activated memory cells was 30%. Thus, chain centricity is an inherent property of some TCRs, but secondary antigenic stimulation can be a factor for selection of clonotypes with such receptors.

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Unique features of the TCR repertoire of reactivated memory T cells in the experimental mouse tumor model

Cited by 2 publications

References 51 publications

T Cell Receptor Chain Centricity: The Phenomenon and Potential Applications in Cancer Immunotherapy

T Cell Receptor Chain Centricity: The Phenomenon and Potential Applications in Cancer Immunotherapy

T-cell receptor chain centricity in the primarily activated effectors and re-stimulated memory cells

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