These studies tested whether antigenic competition between T cells occurs. We generated CD8+ T cell responses in H-2b mice against the dominant ovalbumin epitope SIINFEKL (ova8) and subdominant epitope KRVVFDKL, using either vaccinia virus expressing ovalbumin (VV-ova) or peptide-pulsed dendritic cells. CD8+ T cell responses were visualized by major histocompatibility complex class I–peptide tetrameric molecules. Transfer of transgenic T cells with high affinity for ova8 (OT1 T cells) completely inhibited the response of host antigen-specific T cells to either antigen, demonstrating that T cells can directly compete with each other for response to antigen. OT1 cells also inhibited CD8+ T cell responses to an unrelated peptide, SIYRYGGL, providing it was presented on the same dendritic cells as ova8. These inhibitions were not due to a more rapid clearance of virus or antigen-presenting cells (APCs) by the OT1 cells. Rather, the inhibition was caused by competition for antigen and antigen-bearing cells, since it could be overcome by the injection of large numbers of antigen-pulsed dendritic cells. These results imply that common properties of T cell responses, such as epitope dominance and secondary response affinity maturation, are the result of competitive interactions between antigen-bearing APC and T cell subsets.
Summary: Most old mice and human beings contain large clones of CD8 + αβ TCR + T cells. In mice clones bearing Vβ7 appear more frequently in animals infected with mouse hepatitis virus than in uninfected animals. This property is controlled by some non MHC gene in the animals. The frequency of old mice containing such clones is affected by the origin of the animals. Although the clones are relatively anergic to acute stimuli in vitro, they can divide in vivo since in old animals they divide and turnover with about the same kinetics as other, non‐clonally expanded CD8 + T cells. Moreover the clones expand slowly but inexorably after transfer into recipient animals. These data suggest that the CDS + αβ TCR clones arise because they are specific for some exogenous or auto antigen to which the cells are continuously exposed in vivo.
Superantigens combine with MHC class-II molecules to form the ligands that stimulate T cells via the V β element of the T-cell receptor. Two groups of superantigens have been described so far: first, endogenous murine products that include the MIs determinants, and second, bacterial products such as the Staphylococcal enterotoxins. Here, we review studies that address the interactions between the foreign superantigens and MHC class-II molecules, the mechanism of T-cell stimulation, and the role that tolerance to self -superantigens plays in shaping the T-cell repertoire. We speculate on the possible evolutionary significance of superantigens.
The monoclonal antibody KJ16-133 binds an allelic determinant expressed on the antigen-specific, major histocompatibility complex (MHC)-restricted receptors on approximately 20% of T cells in most mouse strains. The locus controlling the presence or absence of the determinant mapped 9.8 +/- 2.2 centimorgans from the Igk/Ly-2 locus on chromosome 6 in mice, and may be the beta-chain locus. Other genetic loci were identified that controlled the frequency of cells that expressed the allele in positive mice. One of these was the MHC itself, which may control expression of the beta-chain allele by controlling T cell repertoire. The identity of the other, as yet unmapped locus is unknown. KJ16-133 was used to show that T cell receptor gene products are expressed in a manner consistent with allelic exclusion.
