Minor histocompatibility antigen DDX3Y induces HLA-DQ5-restricted T cell responses with limited TCR-Vbeta usage both in vivo and in vitro.
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-Valpha segments. Our results suggest that T cells recognizing the HLA-DQ5/DDX3Y T cell epitope might be characterized by a relatively limited TCR-beta repertoire. The differences in the junctional TCR-beta 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.
Laurin
David
D
Cell Therapy Department, Etablissement Français du Sang Région Rhône-Alpes, Rhône, France.
Spierings
Eric
E
van der Veken
Lars T
LT
Hamrouni
Abdelbasset
A
Falkenburg
J H Frederik
JH
Souillet
Gerard
G
Vermeulen
Corine
C
Farre
Annie
A
Galambrun
Claire
C
Rigal
Dominique
D
Bertrand
Yves
Y
Goulmy
Els
E
Eljaafari
Assia
A
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism; D005260:Female; D005802:Genes, MHC Class II; D019674:Genes, T-Cell Receptor beta / Q000235:genetics*; D006086:Graft vs Host Disease / Q000276:immunology; D006182:H-Y Antigen / Q000235:genetics; D006683:HLA-DQ Antigens / Q000276:immunology*; D006801:Humans; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D015778:Minor Histocompatibility Antigens / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D006182:H-Y Antigen; D006683:HLA-DQ Antigens; C410042:HLA-DQ5 antigen; D015778:Minor Histocompatibility Antigens; C492034:DDX3Y protein, human; D053487:DEAD-box RNA Helicases