Mechanisms and Implications of Immunodominance in CD8+ T-Cell Responses.

Immunodominant Major Histocompatibility Complex class I (MHC I)- associated epitopes suppress T-cell responses against cryptic epitopes. That is, when confronted with complex antigens, CD8+ T cells respond to only a few ˵immunodominant″ epitopes and neglect other ˵cryptic″ peptides that would otherwise be immunogenic when presented alone. Immunodominant epitopes are better immunogens than cryptic epitopes. Compared with T cells specific for cryptic epitopes, CD8+ T cells that recognize immunodominant epitopes interact with their antigen with higher avidity, are primed after a shorter duration of antigen presentation, expand more swiftly and extensively, and generate more potent effector function. Furthermore, by curtailing the duration of Ag presentation [through deletion or exhaustion of antigen presenting cells (APCs)], immunodominant CD8+ effector T cells selectively impair priming against cryptic epitopes. Immunodominance results in one major advantage and one potential drawback: that is, immunodominance favors expansion of the fittest effector T cells but may enhance the risk of immune escape by antigen-loss variants. Targeting immunodominant epitopes is probably crucial not only for success of immune responses against pathogens but also in cancer immunotherapy. Indeed, CD8+ T cells targeted to immunodominant but not cryptic minor histocompatibility antigens can eradicate leukemia and melanoma in mice. In this chapter, I will review the current state-of-the-art regarding T-cell immunodominance and discuss key elements of ongoing and future research in this area. [ABSTRACT FROM AUTHOR]