Protein Tyrosine Phosphatase CD45 As an Immunity Regulator and a Potential Effector of CAR-T therapy
| Dublin Core | PKP Metadata Items | Metadata for this Document | |
| 1. | Title | Title of document | Protein Tyrosine Phosphatase CD45 As an Immunity Regulator and a Potential Effector of CAR-T therapy |
| 2. | Creator | Author's name, affiliation, country | Dmitrii V. Volkov; M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences ; Россия |
| 2. | Creator | Author's name, affiliation, country |
Valeria M. Stepanova; M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences ; Россия |
| 2. | Creator | Author's name, affiliation, country | Yury P. Rubtsov; M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences ; Россия |
| 2. | Creator | Author's name, affiliation, country |
Alexey V. Stepanov; M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences ; Россия |
| 2. | Creator | Author's name, affiliation, country | Alexander G. Gabibov; M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences ; Россия |
| 3. | Subject | Discipline(s) | |
| 3. | Subject | Keyword(s) | CD45; T lymphocytes; B lymphocytes; T cell receptor; cancer; chimeric antigen receptor |
| 4. | Description | Abstract | The leukocyte common antigen CD45 is a receptor tyrosine phosphatase and one of the most prevalent antigens found on the surface of blood cells. CD45 plays a crucial role in the initial stages of signal transmission from receptors of various immune cell types. Immunodeficiency, autoimmune disorders, and oncological diseases are frequently caused by gene expression disorders and imbalances in CD45 isoforms. Despite extensive research into the structure and functions of CD45, the molecular mechanisms behind its role in transmitting signals from T-cell receptors and chimeric antigen receptors remain not fully understood. It is of utmost importance to comprehend the structural features of CD45 and its function in regulating immune system cell activation to study oncological diseases and the impact of CD45 on lymphocytes and T cells modified by chimeric antigen receptors. |
| 5. | Publisher | Organizing agency, location | Acta Naturae Ltd |
| 6. | Contributor | Sponsor(s) |
RSF (17-74-30019) |
| 7. | Date | (DD-MM-YYYY) | 30.10.2023 |
| 8. | Type | Status & genre | Peer-reviewed Article |
| 8. | Type | Type | Review Article |
| 9. | Format | File format | |
| 10. | Identifier | Uniform Resource Identifier | https://actanaturae.ru/2075-8251/article/view/25438 |
| 10. | Identifier | Digital Object Identifier (DOI) | 10.32607/actanaturae.25438 |
| 11. | Source | Title; vol., no. (year) | Acta Naturae; Vol 15, No 3 (2023) |
| 12. | Language | English=en | ru |
| 13. | Relation | Supp. Files |
Fig. 1. The structure and prevalence of CD45 isoforms in blood cells. (A) Six main CD45 isoforms found in humans differ in the composition of their extracellular part owing to the alternative splicing of pre-mRNA of the PTPRC gene; (B) CD45 resides on the membrane of all cells of hematopoietic origin except for platelets and erythrocytes. The amount of CD45 increases during cell differentiation; (C) the structure of CD45RABC. PSC – pluripotent stem cell; A, B, C – the extracellular domains of CD45 responsible for a particular isoform; CR – cysteine-rich region; FNIII – fibronectin type III domains; TM – transmembrane domain; W – wedge domain; D1 – domain with phosphatase activity; D2 – domain required for CD45 to function in the cell (484KB) doi: 10.32607/20758251-2023-15-3-17-26-130053 Fig. 2. The role of CD45 in transmitting T-cell receptor activation signal. T cell activation stages are shown: the pre-active (A), active (B), and post-active (C) ones. During the activation cycle, the composition and phosphorylation of IS participants changes: first (A), Lck kinase exists in the state of basal activity due to dephosphorylation by CD45 phosphatase prevailing over phosphorylation by Csk kinase; in the active state (B), CD45 is “segregated” in dSMAC due to its rigid and bulky structure (long isoforms) and Lck becomes active due to autophosphorylation and prevalence over Csk and phosphorylates CD3ζ, which enables further signaling; short isoforms of CD45 gradually penetrating cSMAC are synthesized at this time, and Csk accumulates there, leading to a transition of Lck to its inactive form and the end of signaling (C). MHCI/II I – major histocompatibility complex class I or II; APC – antigen-presenting cell; PA – presenting antigen; ζ – CD3ζ; TCR – T-cell receptor; Lck, Csk – protein kinases; cSMAC, pSMAC, dSMAC – the central, peripheral, and distal supramolecular activation clusters, respectively (705KB) doi: 10.32607/20758251-2023-15-3-17-26-130054 Fig. 3. The length of the extracellular part of CD45 influences CAR signaling. CD45 segregation from the immune synapse and CAR signaling strength as a result of an increase in the length of the extracellular portion of phosphatase. CAR T cell – T cell modified by the chimeric antigen receptor (224KB) doi: 10.32607/20758251-2023-15-3-17-26-130055 |
| 14. | Coverage | Geo-spatial location, chronological period, research sample (gender, age, etc.) | |
| 15. | Rights | Copyright and permissions |
Copyright (c) 2023 Volkov D.V., Stepanova V.M., Rubtsov Y.P., Stepanov A.V., Gabibov A.G. This work is licensed under a Creative Commons Attribution 4.0 International License. |