CD8 T cell competition for dendritic cellsin vivois an early event in activation

Abstract

T cell responses against an antigen are often focused on a small fraction of potentially immunogenic determinants, a phenomenon known as immunodominance. Immunodominance can be established at several stages of antigen presentation, including antigen processing, binding of peptides to MHC, and competition between T cells for dendritic cells (DCs). The mechanism of this T cell competition is unclear, but may include competition for physical access to DCs, competition for limiting soluble DC-derived factors, or a suppressive effect of one T cell population on the other(s). To model DC-specific T cell competition, normal mice were injected with one or two T cell receptor transgenic CD8 T cell populations, each with high affinity for different peptides presented by different class I MHC complexes. These mice were immunized with DCs pulsed with peptides that are recognized by the transferred T cells. Competition was detectable when both T cell populations were transferred and their target peptides were present on the same DCs. The competition resulted in fewer cells entering the response, but had no effect on the level of activation of the cells that did respond. The effect was evident very early in the response, and in fact the competing T cells needed to be present in the first 5 h of the response for competition to occur. Thus, some aspect of DCs other than peptide/MHC complexes is limiting in the earliest stages of the CD8 T cell response. These results have implications for the design of multivalent vaccines.