ENGRAFTED MATERNAL T-CELLS IN A SEVERE COMBINED IMMUNODEFICIENCY PATIENT EXPRESS T-CELL RECEPTOR VARIABLE BETA-SEGMENTS CHARACTERIZED BY A RESTRICTED V-D-J JUNCTIONAL DIVERSITY

To better understand the peculiar functional behavior of engrafted mat ernal T cells in a severe combined immunodeficiency (SCID) patient, we characterized, at the molecular level, the T-cell repertoire of a SCI D child with a high number of engrafted, mature, activated lymphocytes . We found that, although these transplacentally acquired T cells expr ess a random set of T-cell receptor variable beta (TCRBV) segments, th e TCRBV transcripts are characterized by an extremely restricted V-D-J junctional diversity. Only a few cDNA clones were dominant among the TCRBV4(+), TCRBV6(+), and TCRBV20(+) populations in engrafted cells, w hereas the same TCRBV chains expressed by the mother's lymphocytes had the expected junctional hetero-geneity, Highly diverse and polyclonal junctions were also expressed by maternal cells activated in mixed ly mphocyte reaction by Epstein-Barr virus (EBV)-transformed B lymphocyte s from the patient, indicating that the strong clonal selection that c haracterizes the engrafted cells repertoire is probably not due to all orecognition. Furthermore, we report that the repertoire of the transp lacentally acquired lymphocytes is dynamic over time and is characteri zed by waves of expression and contraction of selected clones, express ing different TCRBV segments. These results help to explain some of th e abnormal functional behaviors of engrafted maternal cells and raise new questions regarding the mechanisms responsible for the restricted clonal diversity. (C) 1995 by The American Society of Hematology.