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

Neutrophil, monocyte, natural killer- and B-cell number and function are ra pidly restored after bone marrow transplant (BMT), whereas T-cell reconstit ution is often quite delayed. Our hypothesis was that V beta T-cell recepto r (TCR) repertoire diversity among recipients of allogeneic BMT is influenc ed by the expression of major and minor HLA antigens in the host. The study population comprised unmanipulated and CD34(+)-selected allogeneic bone ma rrow grafts, autologous peripheral blood stem cell transplants and recipien ts of volunteer unrelated donor (VUD) bone marrow transplants. Using flow c ytometry, the relative frequencies of 18 V beta TCR families were determine d and ranked for each time point studied. Comparisons and correlations were made between paired blood samples obtained within a single patient over ti me, 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 p attern of the V beta TCR repertoire in recipients of HLA-matched sibling tr ansplants 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.