Restricted usage of T‐cell receptor α‐chain variable region (TCRAV) and T‐cell receptor β‐chain variable region (TCRBV) repertoires after human allogeneic haematopoietic transplantation

Abstract

Summary. We analysed T-cell receptor a-chain variable region (TCRAV) and T-cell receptor b-chain variable region (TCRBV) repertoires in peripheral blood mononuclear cells (PBMCs) from 34 recipients of allogeneic bone marrow transplantation (allo-BMT), seven of allogeneic peripheral blood stem cell transplantation and 19 of autologous peripheral blood stem cell transplantation using the quantitative microplate hybridization assay. TCR usage skewed at an early period (6±7 weeks) after BMT. The change was more apparent in allogeneic recipients than in autologous recipients. In particular, a predominant increase was detected in the frequency of VA1-4 (26%, 11 of 41 recipients), VA3-1 (32%) and VB24-1 (28%). Interestingly, acidic amino acid residues frequently followed the arginine residue in complementarity-determining region 3 of BV24S1.We further examined the extent of skew using samples obtained at serial time points after transplantation. The normalization of skewed repertoires occurred over a long period of time (. 8 years). There was a significant difference in the rate of normalization of skewed TCR repertoires between adult and child recipients (P , 0´05). The results suggest that these T cells may have expanded in response to allogeneic antigens, such as miHA (minor histocompatibility antigen), and that altered repertoires are eventually normalized by T-cell regeneration via a thymic-dependent pathway in children.

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

“…2,3 We also found that TCR usage appears to be limited, and that amino acid sequences frequently contain an arginine residue followed by acidic amino acid residues in the complementarity-determining region 3 (CDR3) of TCR-␤ chains containing BV24S1, suggesting that skewing of the TCRAV and TCRBV repertoires is antigen-driven. 1 These features of post-transplant T cell regeneration are similar to those during extrathymic differentiation of T cell progenitors and peripheral expansion of mature T cell populations, which have been demonstrated by murine bone marrow transplantation studies. 4 Extrathymic differentiation of T cell progeny in bone marrow generates TCR␥␦ ϩ and CD4 Ϫ CD8 Ϫ TCR␣␤ ϩ T cells.…”

Distinct TCRAV and TCRBV repertoire and CDR3 sequence of T lymphocytes clonally expanded in blood and GVHD lesions after human allogeneic bone marrow transplantation

“…5,7 In addition, evidence indicates the stable clonal expansion of T lymphocytes after bone marrow transplantation. 30,31 Whether these clonally expanded T cells in blood recognize allogeneic, or microorganism-921 Table 5 Deduced Bone Marrow Transplantation derived antigens remains uncertain.…”

“…[2][3][4] We previously reported a skewing of repertoires of the T cell receptor-␤ chain variable region (TCRBV) and the TCR-␣ chain variable region (TCRAV) in recipients of allogeneic hematopoietic stem cell grafts from HLAmatched donors. 5 This results from the extensive clonal expansion of a limited number of T cells in the graft. 6 Skewed TCR repertoires accompany accumulation of the CD28 Ϫ fraction in both CD4 + and CD8 + T cells.…”

“…5,27 To determine whether skewed TCRAV and TCRBV families are also found in GVHD lesions as well as in peripheral blood, we compared the TCR repertoires of T lymphocytes in GVHD tissues with those in PBMCs from the same individual.…”

“…5,6 To address whether or not the clonally expanded T cells in circulating blood recognize the same antigen as those expanded in GVHD lesions, we compared the usage of TCRAV and TCRBV subfamilies and the CDR3 sequences of clonally expanded T cells from blood and tissues. Since expanded T cells in the blood were not necessarily clonal/oligoclonal, 6 clonality was first determined by TCRBV-CDR3 size spectratyping (Figure 4), then the CDR3 sequences of clonally expanded T cells were analyzed.…”