Transcription profiling of mouse splenocytes reveals immunodomination leads to selective expansion of the fittest CD8 T cells

ABSTRACT: During the course of infection, T cells are confronted with a multitude of non self epitopes but only respond to a few epitopes and neglect other potentially immunogenic peptides. Restriction of T cell responses to a small number of selected epitopes (immunodominance) is a central feature of immune responses. Immunodominance is considered to be disadvantageous to the host because it allows pathogens to escape by selectively mutating the relevant epitope(s). Using Affymetrix microarrays, we compared the gene expression profile of unprimed CD8 T cells to that of effector CD8 T cells specific for a dominant (H7a) and a nondominant (HY) Ag. Our key finding is that T cells specific for the dominant and nondominant Ags displayed similar gene expression profiles except for a few gene transcripts, such as Gzma, Sell, Il7r and Klrg1, that contribute to the fitness of effector CD8 T cells. The differences between HY- and H7a-specific CD8 T cells were validated by real-time PCR and flow cytometry analyses. We propose that, by leading to selective expansion of the fittest CD8 effector T cells, immunodominance may be beneficial to the host. Inhibition of T cell response to nondominant Ags would ensure that host resources (APCs, cytokines) for which T cells compete are devoted to T cells that have the best effector potential. One implication is that, in general, favouring expansion of the fittest effector T cells may be more important that increasing the diversity of the T cell repertoire. Experiment Overall Design: B10.H7b female mice were primed by i.p. injection of a cell mixture containing 2 x 107 B10 male splenocytes and 2 x 107 B10.H7b male splenocytes. On day 14 after priming, splenocytes were labeled with anti-CD8 Ab as well as H7a- and HY-Tet labeled with different fluorochromes. Then, three populations of splenocytes were purified using a FACS cell sorting: HYTet+ (n=4), H7aTet+ (n=4), and Tet- (n=5) CD8 T cells. RNA of sorted T cells was extracted and linearly amplified, cRNA was prepared, and Affymetrix Mouse Genome 430 2.0 oligonucleotide arrays were used to analyze gene expression.

ORGANISM(S): Mus musculus

SUBMITTER: Etienne Caron 

PROVIDER: E-GEOD-2924 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress