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Lymphoid Reconstitution

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

Abstract

We previously described skewed repertoires of the T cell receptor-β chain variable region (TCRBV) and the TCR-α 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. Bone Marrow Transplantation (2001) 27, 607–614.

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Acknowledgements

We are grateful to the hematology staff at Akita University Medical Center for assistance with the patients included in this study. This work was supported by grants from the Ministry of Education, Science, Sports and Culture of Japan (Grant No. 08670508, 10670932), the Yamashita Taro-Kensho Memorial Foundation and the Uehara Memorial Foundation.

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Hirokawa, M., Matsutani, T., Horiuchi, T. et al. 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. Bone Marrow Transplant 27, 607–614 (2001). https://doi.org/10.1038/sj.bmt.1702858

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