Memory TCR repertoires analyzed long-term reflect those selected during the primary response

Normal T cell repertoire selection and evolution in antigen-specific responses is poorly understood. We have recently described an MHC class I-restricted response characterized by an overwhelming expansion of CD8 cells expressing a Vbeta10 TCR, thus allowing the identification of antigen-selected cells directly ex vivo. Our present strategy to follow the overall TCR repertoire selection was to monitor the expression of a particular TCR alpha chain (Valpha8) on antigen-selected Vbeta10(+) cells by four-color flow cytometry. We demonstrate that while there is substantial variation among the responder mice in Valpha8 usage, the repertoires of individual animals remain relatively stable over long periods of time (>1 year), with or without repeated antigenic challenge. Thus if any evolution of this response occurs upon re-exposure to antigen, it would appear not to skew the TCR repertoire established during the primary response.