Restricted usage of T-cell receptor alpha-chain variable region (TCRAV) and T-cell receptor beta-chain variable region (TCRBV) repertoires after human allogeneic haematopoietic transplantation

We analysed T-cell receptor alpha-chain variable region (TCRAV) and T-cell receptor beta-chain variable region (TCRBV) repertoires in peripheral blood mononuclear cells (PBMCs) from 34 recipients of allogeneic bone marrow tra nsplantation (allo-BMT), seven of allogeneic peripheral blood stem cell tra nsplantation and 19 of autologous peripheral blood stem cell transplantatio n using the quantitative microplate hybridization assay. TCR usage skewed a t an early period (6-7 weeks) after BMT. The change was more apparent in al logeneic recipients than in autologous recipients. In particular, a predomi nant increase was detected in the frequency of VA1-4 (26%, 11 of 41 recipie nts), VA3-1 (32%) and VB24-1 (28%). Interestingly, acidic amino acid residu es frequently followed the arginine residue in complementarity-determining region 3 of BV24S1. We further examined the extent of skew using samples ob tained at serial time points after transplantation. The normalization of sk ewed repertoires occurred over a long period of time (> 8 years). There was a significant difference in the rate of normalization of skewed TCR repert oires between adult and child recipients (P < 0.05). The results suggest th at these T cells may have expanded in response to allogeneic antigens, such as miHA (minor histocompatibility antigen), and that altered repertoires a re eventually normalized by T-cell regeneration via a thymic-dependent path way in children.