Identification of HLA class I dependent immunogenic peptides from clonotypic TCRβ expressed in cutaneous T‐cell lymphoma

Abstract

The clonotypic T-cell receptor (TCR) is a potential target antigen for specific immunotherapy of cutaneous T-cell lymphoma (CTCL). We identified T-cell epitopes from the rearranged TCR b chain of the malignant T-cell population by the ''reverse immunology'' approach. Peptide-specific T-cell lines were generated against predicted epitopes and tested for the recognition of tumor cells and cells transfected with the full-length DNA coding for TCRV b chain. Two peptides derived from the clonotypic TCRVb of a HLA-A2 positive patient could induce peptide-specific T cells from peripheral blood mononuclear cells of healthy donors and the patient as assessed by IFN-c ELISpot assay. Furthermore, the reactive CTLs efficiently recognized autologous S ezary tumor cells, as well as HLA-A2 positive 293 cells transfected with recombinant plasmid expressing the corresponding TCRVb29 protein. Similar results were obtained in a HLA-A31 patient for TCRVb7-Jb2.7. In conclusion, our experiments show that the TCR b chain harbors epitopes suitable as targets for specific vaccination which might be a promising approach for the specific immunotherapy of cutaneous T-cell lymphoma patients. ' 2006 Wiley-Liss, Inc.

mRNA-Based Anti-TCR CDR3 Tumour Vaccine for T-Cell Lymphoma

“…This type of vaccination can be advantageously combined with immune checkpoint inhibitors currently under evaluation in T-lymphomas [ 37 , 38 , 39 , 40 ] or established immunomodulatory approaches, especially interferon-alpha [ 41 , 42 ]. The possibility of vaccinating against the TCR to treat CTCL is further supported by other reports: Berger et al [ 43 ], Zheng et al [ 44 ] and Winter et al [ 45 ] have shown that MHC class I epitopes derived from TCR chains expressed in human CTCL can be recognised by cytotoxic T-cells. Besides the intra-venous injection of liposomes bringing the unmodified (immunostimulating) mRNA to lymphoid organs as disclosed in mice and humans by Kranz et al [ 12 ] and used here, the COVID-19 pandemic has seen the emergency approval of two formulations of modified (PseudoUridine: immunosilent mRNA) mRNA for intramuscular injections [ 11 , 46 ].…”

Observations of TCRVβ Gene Expression in Rats with Dampness Syndrome

“…Engagement of the TCR with an antigen and MHC results in activation of its T lymphocyte through a series of biochemical events mediated by associated enzymes, coreceptors, and specialized accessory molecules. TCR V β T cells are the major subset of T cells [ 18 , 19 ]. An analysis of T-cell receptor variable gene repertoires might provide important information about the immune response to pathogens or immunopathological mechanisms.…”

Durable Remission of Sézary Syndrome after Unrelated Bone Marrow Transplantation by Reduced-Intensity Conditioning

“…The efficacy of immunomodulatory therapies for MF and SS, such as systemic cytokines, fusion toxins and extracorporeal photopheresis, suggests that this disease can be controlled by an immunological mechanism [24,25,26]. Tumor cells of MF and SS have been shown to express specific human leukocyte antigen class I peptides recognized by cytotoxic T lymphocytes [27, 28]. …”