T-CELL RECEPTOR GERMLINE GENE SEGMENTS AND HLA HAPLOTYPES CONTROL THELENGTH OF THE CDR3 OF HUMAN T-CELL RECEPTOR-BETA CHAINS

The third complementarity determining region (CDR3) is the most variab le part of alpha beta T cell receptors (TCR) and represents the putati ve antigen contacting site, To identify parameters determining the str uctural diversity of the CDR3 region, the CDR3 length distributions of 66 BV-J combinations in peripheral CD4(+) T cells (6 BV and fl BJ gen e segments) of 12 unrelated individuals were analyzed. The median CDR3 length ranged from 8 to 12.5 amino acids and was partially determined by the usage of the BV and BJ gene segment. Beyond the influence of g ermline-encoded TCR gene segments, donors expressed an individual patt ern of preferred CDR3 size classes, To identify mechanisms determining this individual pattern, 17 first-degree relatives from five families were studied, CDR3 length profiles were shared by some but not all re latives, Sharing of CDR3 length profiles correlated with the inheritan ce of both HLA-DR haplotypes. These data suggest that the length of th e TCR beta chain is selected and that restrictions on the diversity of the CDR3 length are imposed by germline-encoded TCR gene segments as well as by major histocompatibility complex-dependent mechanisms. (C) 1996 Academic Press, Inc.