T cell receptor germline gene segments and HLA haplotypes control the length of the CDR3 of human T cell receptor beta chains.
The third complementarity determining region (CDR3) is the most variable part of alpha beta T cell receptors (TCR) and represents the putative antigen contacting site. To identify parameters determining the structural diversity of the CDR3 region, the CDR3 length distributions of 66 BV-J combinations in peripheral CD4+ T cells (6 BV and ll BJ gene 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 germline-encoded TCR gene segments, donors expressed an individual pattern 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 relatives. Sharing of CDR3 length profiles correlated with the inheritance of both HLA-DR haplotypes. These data suggest that the length of the 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.
Kayser
C
C
Department of Medicine, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
Waase
I
I
Weyand
C M
CM
Goronzy
J J
JJ
D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry*; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000235:genetics*; D016415:Sequence Alignment
D016693:Receptors, Antigen, T-Cell, alpha-beta