Genes encoded within the major histocompatibility complex (MHC) and T cell antigen receptor (TCR) gene complexes play important roles in immune responses and in susceptibility to autoimmune diseases. The contribution of individual gene products within these gene complexes and the mechanisms by which they function remain obscure. In the present studies, the extent of the germline TCRB repertoire was defined and diversity of T cells in certain immune responses was characterized. Examination of the germline TCRBV repertoire revealed 64 genes of which 51 are functional. Polymorphic gene segments and regions within the gene complex showing genetic variation were identified; these include two frequently occurring insertion/deletion related polymorphisms (IDRP). The IDRP located in the TCRBV region contained three genes; BV7S3, BV9S2(P), and a second, identical, copy of BV13S2. The inserted region is >98% identical to a segment present in all individuals which suggests that genetic mechanisms for its origin may include unequal crossing over, gene conversion like events, insertion and deletion of short segments of DNA and mutation. Six orphon BV genes were mapped to chromosome 9 outside of the gene complex. The orphon genes and seven genes encoded within the TCRB gene complex are pseudogenes and three BV genes were found to have null or nonfunctional alleles. The utilized TCR repertoire was examined by analysis of CDR3 length diversity (spectratyping), sequencing, and semiquantitative PCR as well as by the use of monoclonal antibodies to TCRV chains. T cells responding to Hepatitis B surface antigen showed oligoclonal populations of T cells for several BV families. The predominant BV families and CDR3 lengths used were similar among different responder individuals. Activated cells from patients with autoimmune diseases were analyzed in a similar fashion. Patients with Kawasaki's disease showed restricted expansion of T cells. Several TCRBV families had one predominant CDR3 length; however, sequence analysis indicated significant sequence diversity. Detailed knowledge of the extent and diversity of the germline TCR repertoire will greatly facilitate our ability to understand the role of TCR genes in immune responses in normal and disease states.
