Longitudinal analysis of T cells responding to tetanus toxoid in healthy subjects as well as in pediatric patients after bone marrow transplantation: the identification of identical TCR-CDR3 regions in time suggests long-term stability of at least part of the antigen-specific TCR repertoire.
To understand the nature of long-term Th immune responses, we investigated in the present study the TCRBV gene repertoire of CD4(+) T cells specific for the recall antigen tetanus toxoid (TT) in recipients of an allogeneic bone marrow transplantation (allo-BMT) at several time points after transplantation and in their BM donors. We observed that the TCR repertoire of TT-specific CD4(+) Th cells was heterogeneous, and differed between allo-BMT recipients and their respective donors. Some individuals, however, used similar TCR-complementarity-determining region (CDR) 3 motifs that could reflect recognition of and selection by similar promiscuous epitopes of TT. Longitudinal analysis of this TT-specific T cell response revealed that T cells with completely identical TCR were present at several time points after the first analysis in allo-BMT recipients, most probably reflecting long-term stability of at least part of the antigen-specific TCR repertoire. Similar stability of the TT-specific TCR repertoire in time was also noted in the allo-BMT donors. These observations reveal that within a given individual the dominant antigen-specific T cell clones persist in time in an otherwise diverse TT-specific CD4(+) T cell immune response.
Department of Pediatrics, Leiden University Medical Center, Building 1, E3-Q, PO Box 9600, 2300 RC Leiden, The Netherlands.
B C
BC
Godthelp
M J
MJ
van Tol
J M
JM
Vossen
P J
PJ
van den Elsen
D016026:Bone Marrow Transplantation / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D002999:Clone Cells; D022801:Complementarity Determining Regions / Q000235:genetics*; D006410:Hematopoiesis / Q000276:immunology; D006801:Humans; D008137:Longitudinal Studies; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D016511:Severe Combined Immunodeficiency / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology*; D014184:Transplantation, Homologous
D022801:Complementarity Determining Regions; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013745:Tetanus Toxoid