Extensive clonal expansion of T lymphocytes causes contracted diversity of complementarity-determining region 3 and skewed T cell receptor repertoires after allogeneic hematopoietic cell transplantation.
We previously described skewed repertoires of the T cell receptor-beta chain variable region (TCRBV) and the TCR-alpha chain variable region (TCRAV) soon after allogeneic hematopoietic cell transplantation. To determine the characteristics of skewed TCRBV after transplantation, we examined the clonality of T lymphocytes carrying skewed TCRBV subfamilies and determined the CDR3 sequences of expanded T cell clones. In all 11 recipients examined, TCR repertoires were skewed, with an increase of certain TCRBV subfamilies that differed among individuals. In nine of 11 patients, clonal/oligoclonal T cell expansion was observed, although the expanded T cells were not necessarily oligoclonal. The extent of expansion after transplantation appeared to predict clonality. The arginine (R)-X-X-glycine (G) sequence was identified in clonally expanded T cells from four of five recipients examined, and glutamic acid (E), aspartic acid (D) and alanine (A) were frequently inserted between R and G. These results suggest that T lymphocyte expansion may result from the response to antigens widely existing in humans, and that the extensive clonal expansion of a limited number of T cells leads to contracted CDR3 diversity and post-transplant skewed TCR repertoires.
Hirokawa
M
M
Department of Internal Medicine III, Akita University School of Medicine, Akita, Japan.
Matsutani
T
T
Horiuchi
T
T
Kawabata
Y
Y
Kitabayashi
A
A
Yoshioka
T
T
Tsuruta
Y
Y
Suzuki
R
R
Miura
A B
AB
D002999:Clone Cells / Q000276:immunology; D022801:Complementarity Determining Regions / Q000235:genetics*; D016384:Consensus Sequence; D017931:DNA Primers; D019674:Genes, T-Cell Receptor beta; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology*
D022801:Complementarity Determining Regions; D017931:DNA Primers; D011948:Receptors, Antigen, T-Cell