Activation and Detection of HTLV-I Tax-specific CTLs by Epitope Expressing Single-chain Trimers of MHC Class I in a Rat Model

Overview

Journal Retrovirology

Publisher Biomed Central

Specialty Microbiology

Date 2008 Oct 9

PMID 18840303

Citations 4

Authors

Takashi Ohashi

Mika Nagai

Hiroyuki Okada

Ryo Takayanagi

Hisatoshi Shida

Affiliations

Soon will be listed here.

Abstract

Background: Human T cell leukemia virus type I (HTLV-I) causes adult T-cell leukemia (ATL) in infected individuals after a long incubation period. Immunological studies have suggested that insufficient host T cell response to HTLV-I is a potential risk factor for ATL. To understand the relationship between host T cell response and HTLV-I pathogenesis in a rat model system, we have developed an activation and detection system of HTLV-I Tax-specific cytotoxic T lymphocytes (CTLs) by Epitope expressing Single-Chain Trimers (SCTs) of MHC class I.

Results: We have established expression vectors which encode SCTs of rat MHC-I (RT1.Al) with Tax180-188 peptide. Human cell lines transfected with the established expression vectors were able to induce IFN-gamma and TNF-alpha production by a Tax180-188-specific CTL line, 4O1/C8. We have further fused the C-terminus of SCTs to EGFP and established cells expressing SCT-EGFP fusion protein on the surface. By co-cultivating the cells with 4O1/C8, we have confirmed that the epitope-specific CTLs acquired SCT-EGFP fusion proteins and that these EGFP-possessed CTLs were detectable by flow cytometric analysis.

Conclusion: We have generated a SCT of rat MHC-I linked to Tax epitope peptide, which can be applicable for the induction of Tax-specific CTLs in rat model systems of HTLV-I infection. We have also established a detection system of Tax-specific CTLs by using cells expressing SCTs fused with EGFP. These systems will be useful tools in understanding the role of HTLV-I specific CTLs in HTLV-I pathogenesis.

Citing Articles

HTLV-1 Tax Tug-of-War: Cellular Senescence and Death or Cellular Transformation.

Bellon M, Nicot C Pathogens. 2024; 13(1).

PMID: 38276160 PMC: 10820833. DOI: 10.3390/pathogens13010087.

Combined cytolytic effects of a vaccinia virus encoding a single chain trimer of MHC-I with a Tax-epitope and Tax-specific CTLs on HTLV-I-infected cells in a rat model.

Ohashi T, Nakamura T, Kidokoro M, Zhang X, Shida H Biomed Res Int. 2014; 2014:902478.

PMID: 24791004 PMC: 3985193. DOI: 10.1155/2014/902478.

Properties and applications of single-chain major histocompatibility complex class I molecules.

Kotsiou E, Brzostek J, Gould K Antioxid Redox Signal. 2010; 15(3):645-55.

PMID: 21126187 PMC: 3125553. DOI: 10.1089/ars.2010.3694.

Basic and translational applications of engineered MHC class I proteins.

Hansen T, Connolly J, Gould K, Fremont D Trends Immunol. 2010; 31(10):363-9.

PMID: 20832361 PMC: 2949479. DOI: 10.1016/j.it.2010.07.003.

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