Genes encoded within the major histocompatibility complex (MHC) and T cell antigen receptor (TCR) gene complexes have been shown to 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 order to study T cell responses, the TCR repertoire expressed by peripheral blood T lymphocytes of healthy individuals was determined. This was accomplished by display of the diversity in TCR CDR3 lengths (spectratype analysis) and by sequence analyses of TCR transcripts. The lengths of CDR3 regions of TCR from each of the TCRB variable families were normally distributed with a range of 6-18 amino acids. T cells stimulated in vitro with agents such as mitogens, superantigens or nominal antigens displayed distinctive patterns of CDR3 length heterogeneity for the TCRBV families. Responses to mitogens are polyclonal and involve T cells expressing all TCRBV families. Spectratype profiles of PHA stimulated T cells closely resemble PBL patterns. Nominal antigens elicited a T cell response involving oligoclonal expansions within most TCRBV families. The response to a superantigen resulted not only in the polyclonal expansion of selected TCRBV families as well as oligoclonal expansions of most other TCRBV families. The T cell response to Hepatitis B surface antigen (HBsAg) is stable over extended periods of time, clonotypic and involves multiple TCRBV families. T cell lines (TCL) responding to HBsAg have restricted patterns of CDR3 lengths for most TCRBV families. Identical spectratype profiles were observed for >80% of the TCRBV families in two TCL derived from the same donor one year apart. TCRBV with restricted CDR3 lengths correspond to clonotypic T cell expansions. Detailed knowledge of the extent and diversity of the TCR repertoire used in specific immune responses will facilitate our ability to understand the role of TCR genes in immune responses in normal and disease states.
