Cell-mediated immunity stems from the proliferation of naive T lymphocytes expressing T cell antigen receptors (TCRs) specific for foreign peptides bound to host major histocompatibility complex (MHC) molecules. Because of the tremendous diversity of the T cell repertoire, naive T cells specific for any one peptide:MHC complex (pMHC) are extremely rare. Thus, it is not known how many naive T cells of any given pMHC specificity exist in the body or how that number influences the immune response. By using soluble pMHC class II (pMHCII) tetramers and magnetic bead enrichment, we found that three different pMHCII-specific naive CD4+ T cell populations vary in frequency from 20 to 200 cells per mouse. Moreover, naive population size predicted the size and TCR diversity of the primary CD4+ T cell response after immunization with relevant peptide. Thus, variation in naive T cell frequencies can explain why some peptides are stronger immunogens than others.
|Original language||English (US)|
|Number of pages||11|
|State||Published - Aug 24 2007|
Bibliographical noteFunding Information:
We thank K. Hogquist and D. Mueller for helpful discussions and J. Walter for technical assistance. This work was supported by grants from the National Institutes of Health (to J.J.M. and M.K.J.). The authors declare that they have no competing financial interests.