THE HUMAN T-CELL RECEPTOR BETA-CHAIN REPERTOIRE - LONGITUDINAL FLUCTUATIONS AND ASSESSMENT IN MHC MATCHED POPULATIONS

The influence of the environment and of the major histocompatibility c omplex (MHC) in shaping the human T-cell receptor beta-chain variable region (TCRBV) repertoire has not been systematically studied. Here, e xpression of TCRBV gene families was estimated by a sensitive polymera se chain reaction (PCR)-based method. Serial studies of peripheral blo od, performed at 2-week intervals over a 3-month period, revealed that fluctuation in the expression of many TCRBV genes occurred in healthy individuals and in the absence of clinically evident infections. Fluc tuation of TCRBV4, TCRBV5.2, TCRBV9, and TCRBV13.1 genes were present in all subjects. Additional TCRBV genes fluctuated in some but not in other individuals. Comparison of the TCRBV repertoire between these un related individuals indicated differences in the mean expression of TC RBV5.1, TCRBV9, TCRBV11, TCRBV1.5, TCRBV17, and TCRBV20 genes. For any TCRBV gene, intersubject differences were generally of a magnitude of twofold or less. Larger differences characterized the TCRBV repertoir e of CD4 compared to CD8 cells. Some differences, for example over-rep resentation of TCRBV2 and TCRBV5.1 on CD4, and TCRBV10, TCRBV14, and T CRBV16 on CD8 cells, were present in most subjects. Individuals homozy gous for DR2- or DR3-bearing extended MHC haplotypes displayed similar individual variability of TCRBV expression. These data indicate that the circulating TCRBV repertoire in humans is both dynamic and diverse . Both environment and MHC effects contribute to the diversity of TCRB V expression.