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. 2001 Mar;27(6):607-14. doi: 10.1038/sj.bmt.1702858.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Clone Cells / immunology
  • Complementarity Determining Regions / genetics*
  • Consensus Sequence
  • DNA Primers
  • Genes, T-Cell Receptor beta
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Lymphocyte Activation / immunology*
  • Polymerase Chain Reaction
  • Receptors, Antigen, T-Cell / genetics*
  • T-Lymphocytes / immunology*
  • Transplantation, Homologous / immunology*

Substances

  • Complementarity Determining Regions
  • DNA Primers
  • Receptors, Antigen, T-Cell