T cell receptor repertoire analysis in HTLV-1-associated diseases
Human T lymphotropic virus 1 (HTLV-1) is a human retrovirus identified as the causative agent in adult T-cell leukemia/lymphoma (ATL) and chronic-progressive neuroinflammatory disorder HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 is estimated to infect between 5-20 mil...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.984274/full |
| _version_ | 1811261822057054208 |
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| author | Annaliese Clauze Yoshimi Enose-Akahata Steven Jacobson |
| author_facet | Annaliese Clauze Yoshimi Enose-Akahata Steven Jacobson |
| author_sort | Annaliese Clauze |
| collection | DOAJ |
| description | Human T lymphotropic virus 1 (HTLV-1) is a human retrovirus identified as the causative agent in adult T-cell leukemia/lymphoma (ATL) and chronic-progressive neuroinflammatory disorder HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 is estimated to infect between 5-20 million people worldwide, although most infected individuals remain asymptomatic. HTLV-1 infected persons carry an estimated lifetime risk of approximately 5% of developing ATL, and between 0.25% and 1.8% of developing HAM/TSP. Most HTLV-1 infection is detected in CD4+ T cells in vivo which causes the aggressive malignancy in ATL. In HAM/TSP, the increase of HTLV-1 provirus induces immune dysregulation to alter inflammatory milieu, such as expansion of HTLV-1-specific CD8+ T cells, in the central nervous system of the infected subjects, which have been suggested to underlie the pathogenesis of HAM/TSP. Factors contributing to the conversion from asymptomatic carrier to disease state remain poorly understood. As such, the identification and tracking of HTLV-1-specific T cell biomarkers that may be used to monitor the progression from primary infection to immune dysfunction and disease are of great interest. T cell receptor (TCR) repertoires have been extensively investigated as a mechanism of monitoring adaptive T cell immune response to viruses and tumors. Breakthrough technologies such as single-cell RNA sequencing have increased the specificity with which T cell clones may be characterized and continue to improve our understanding of TCR signatures in viral infection, cancer, and associated treatments. In HTLV-1-associated disease, sequencing of TCR repertoires has been used to reveal repertoire patterns, diversity, and clonal expansions of HTLV-1-specific T cells capable of immune evasion and dysregulation in ATL as well as in HAM/TSP. Conserved sequence analysis has further been used to identify CDR3 motif sequences and exploit disease- or patient-specificity and commonality in HTLV-1-associated disease. In this article we review current research on TCR repertoires and HTLV-1-specific clonotypes in HTLV-1-associated diseases ATL and HAM/TSP and discuss the implications of TCR clonal expansions on HTLV-1-associated disease course and treatments. |
| first_indexed | 2024-04-12T19:12:49Z |
| format | Article |
| id | doaj.art-ad565944f6334816bec2c61bdd050b78 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T19:12:49Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-ad565944f6334816bec2c61bdd050b782022-12-22T03:19:50ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-09-011310.3389/fimmu.2022.984274984274T cell receptor repertoire analysis in HTLV-1-associated diseasesAnnaliese ClauzeYoshimi Enose-AkahataSteven JacobsonHuman T lymphotropic virus 1 (HTLV-1) is a human retrovirus identified as the causative agent in adult T-cell leukemia/lymphoma (ATL) and chronic-progressive neuroinflammatory disorder HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 is estimated to infect between 5-20 million people worldwide, although most infected individuals remain asymptomatic. HTLV-1 infected persons carry an estimated lifetime risk of approximately 5% of developing ATL, and between 0.25% and 1.8% of developing HAM/TSP. Most HTLV-1 infection is detected in CD4+ T cells in vivo which causes the aggressive malignancy in ATL. In HAM/TSP, the increase of HTLV-1 provirus induces immune dysregulation to alter inflammatory milieu, such as expansion of HTLV-1-specific CD8+ T cells, in the central nervous system of the infected subjects, which have been suggested to underlie the pathogenesis of HAM/TSP. Factors contributing to the conversion from asymptomatic carrier to disease state remain poorly understood. As such, the identification and tracking of HTLV-1-specific T cell biomarkers that may be used to monitor the progression from primary infection to immune dysfunction and disease are of great interest. T cell receptor (TCR) repertoires have been extensively investigated as a mechanism of monitoring adaptive T cell immune response to viruses and tumors. Breakthrough technologies such as single-cell RNA sequencing have increased the specificity with which T cell clones may be characterized and continue to improve our understanding of TCR signatures in viral infection, cancer, and associated treatments. In HTLV-1-associated disease, sequencing of TCR repertoires has been used to reveal repertoire patterns, diversity, and clonal expansions of HTLV-1-specific T cells capable of immune evasion and dysregulation in ATL as well as in HAM/TSP. Conserved sequence analysis has further been used to identify CDR3 motif sequences and exploit disease- or patient-specificity and commonality in HTLV-1-associated disease. In this article we review current research on TCR repertoires and HTLV-1-specific clonotypes in HTLV-1-associated diseases ATL and HAM/TSP and discuss the implications of TCR clonal expansions on HTLV-1-associated disease course and treatments.https://www.frontiersin.org/articles/10.3389/fimmu.2022.984274/fullhuman T lymphotropic virus 1adult T-cell leukemia/lymphomaHTLV-1-associated myelopathy/tropical spastic paraparesisT cell receptor (TCR)TCR repertoire |
| spellingShingle | Annaliese Clauze Yoshimi Enose-Akahata Steven Jacobson T cell receptor repertoire analysis in HTLV-1-associated diseases Frontiers in Immunology human T lymphotropic virus 1 adult T-cell leukemia/lymphoma HTLV-1-associated myelopathy/tropical spastic paraparesis T cell receptor (TCR) TCR repertoire |
| title | T cell receptor repertoire analysis in HTLV-1-associated diseases |
| title_full | T cell receptor repertoire analysis in HTLV-1-associated diseases |
| title_fullStr | T cell receptor repertoire analysis in HTLV-1-associated diseases |
| title_full_unstemmed | T cell receptor repertoire analysis in HTLV-1-associated diseases |
| title_short | T cell receptor repertoire analysis in HTLV-1-associated diseases |
| title_sort | t cell receptor repertoire analysis in htlv 1 associated diseases |
| topic | human T lymphotropic virus 1 adult T-cell leukemia/lymphoma HTLV-1-associated myelopathy/tropical spastic paraparesis T cell receptor (TCR) TCR repertoire |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.984274/full |
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