Minor Histocompatibility Antigen DDX3Y Induces HLA-DQ5-Restricted T Cell Responses with Limited TCR-Vβ Usage Both In Vivo and In Vitro

Abstract : In vitro stimulation of human female T cells with male HLA-identical dendritic cells resulted in the generation of HLA-DQB1*0501/0502-restricted minor histocompatibility H-Y antigen-specific CD4+ T cell clones. Two clones generated from different HLA-identical pairs were analyzed. Use of HLA-DQ5-expressing female Epstein-Barr virus transformed B lymphoblastoid cell lines transfected with various H-Y genes and loaded with overlapping peptides demonstrated that both T cell clones are specific for a peptide encoded by DDX3Y. Previously, an HLA-DQ5-restricted T cell clone specific for the same peptide was isolated from a patient with graft-versus-host disease. Thus, we compared the T cell receptor (TCR) rearrangements of the 2 in vitro generated T cell clones and the ex vivo isolated T cell clone. All 3 clones shared the same TCRBV5-4* gene segment and 2 of 3 clones also used similar TCR-Vα segments. Our results suggest that T cells recognizing the HLA-DQ5/DDX3Y T cell epitope might be characterized by a relatively limited TCR-β repertoire. The differences in the junctional TCR-β region had no effect on the antigen specificity, but altered the capacity of the TCR to distinguish the HLA-DQ5/DDX3Y complex from its allelic counterpart. The results also demonstrate that in vitro stimulation of T cells with allogeneic HLA-identical dendritic cells may facilitate the characterization of in vivo, potentially relevant HLA class II-restricted minor H epitopes.
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Submitted on : Monday, January 14, 2019 - 5:44:47 PM
Last modification on : Thursday, February 7, 2019 - 4:05:46 PM

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David Laurin, Eric Spierings, Lars van der Veken, Abdelbasset Hamrouni, J.H. Frederik Falkenburg, et al.. Minor Histocompatibility Antigen DDX3Y Induces HLA-DQ5-Restricted T Cell Responses with Limited TCR-Vβ Usage Both In Vivo and In Vitro. Biology of Blood and Marrow Transplantation, Elsevier, 2006, 12 (11), pp.1114-1124. ⟨10.1016/j.bbmt.2006.07.012⟩. ⟨hal-01980972⟩

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