Genes encoded within the major histocompatibility complex (MHC) and T cell antigen receptor (TCR) alpha and beta chain 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. The ability to produce antibodies to Hepatitis B surface antigen (HBsAg), a widely used vaccine, is genetically controlled, involves T lymphocytes and is associated with certain MHC antigens. High resolution HLA typing for MHC Class I and Class II antigens was performed on individuals who are responders or nonresponders to HBsAg. Several T cell epitopes of HBsAg were identified and T cell clones to peptides were developed. In order to characterize the T cells that recognize HBsAg, the TCR repertoire was examined by spectratype analysis, a technique that displays diversity in TCR CDR3 lengths and by sequence analyses of TCR transcripts. T cell lines (TCL) responding to HBsAg have broad and diverse patterns of TCRBV usage. Transcripts with restricted CDR3 lengths were observed for most TCRBV families and no conserved sequence motifs in CDR3 regions were apparent. PBMC samples showed normally distributed spectratype patterns for most of the 30 TCRA families analyzed. However, spectratype profiles for certain VA families were skewed and showed expansion of transcripts having a single CDR3 length. Examination of isolated CD4+, CD8+, and CD4-8- (DN) T cell subpopulations revealed that the skewed profiles could be attributed principally to DN and CD8+ T cell subpopulations. DN populations from multiple individuals showed distinctive patterns of expanded TCR specifically in the AV7, AV24, and AV19 families with common CDR3 sizes. These data suggest a specialized function for these DN cells. 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.
