Changes in the pattern of TCR V beta repertoire expression after bone marrow transplant is linked to the HLA...

Neutrophil, monocyte, natural killer- and B-cell number and function are rapidly restored after bone marrow transplant (BMT), whereas T-cell reconstitution is often quite delayed. Our hypothesis was that V beta T-cell receptor (TCR) repertoire diversity among recipients of allogeneic BMT is influenced by the expression of major and minor HLA antigens in the host. The study population comprised unmanipulated and CD34(+)-selected allogeneic bone marrow grafts, autologous peripheral blood stem cell transplants and recipients of volunteer unrelated donor (VUD) bone marrow transplants. Using flow cytometry, the relative frequencies of 18 V beta TCR families were determined and ranked for each time point studied. Comparisons and correlations were made between paired blood samples obtained within a single patient over time, and between donors and their recipients. The pattern of the V beta TCR repertoire from allogeneic recipients and their HLA-matched donors was very similar, with a correlation coefficient (CC) of 0.59. This similarity was not as marked in VUD pairs (CC = 0.32). By 3 months after transplant, the pattern of the V beta TCR repertoire in recipients of HLA-matched sibling transplants was more similar to the pattern seen in pretransplant recipients than to the donor pattern (CC = 0.40 vs. 0.31). Our data suggest that both major and minor HLA antigens influence V beta TCR repertoire diversity and reconstitution after BMT.