N. Kienzle et al., Differential splicing of antigen-encoding RNA reduces endogenous epitope presentation that regulates the expansion and cytotoxicity of T cells, J IMMUNOL, 165(4), 2000, pp. 1840-1846
The activation of CTLs is dependent on the recognition of MHC-bound peptide
present on the surface of APCs, We give evidence in this study that differ
ential splicing of Ag-encoding RNA can decrease the antigenic dose in APCs
and regulate the recall of human memory CTLs, Differential splicing of RNA
that encoded an immunodominant HLA-BS-restricted CTL epitope of EBV reduced
the functional presentation of this epitope, and consequently the in vitro
expansion and activity of CTLs, as measured by MHC/peptide-tetramer staini
ng and cytotoxicity assays. The reduced activity of the stimulated CTLs was
not only due to lower numbers of Ag-specific CTLs but, surprisingly, was a
lso characterized by decreased cytotoxicity of the CTLs to target cells pre
senting limiting amounts of the peptide epitope, As indicated by TCR repert
oire analysis, the reduction in CTL activity was not caused by stimulation
of distinct populations of TCR clonotypes, This study demonstrates how a co
mmon eukaryotic posttranscriptional mechanism of gene regulation can modula
te the endogenous presentation of Ag and ultimately contribute to the fine
tuning of immunological memory cells, which are important In the fight agai
nst pathogens and tumors and in autoimmunity.