Immunodominance

Immunodominance is a phenomenon in adaptive immunity in which among multiple potential epitopes of an antigen presented by MHC molecules, a limited subset elicits the majority of T cell responses. This can involve CD8+ cytotoxic T lymphocytes recognizing peptide-MHC class I complexes as well as CD4+ helper T cells recognizing peptide-MHC class II complexes. B cell responses may also concentrate on a few available epitopes, giving rise to immunodominant antibody specificities. Immunodominance contributes to the overall magnitude and specificity of immunity and can influence the breadth of responses to pathogens and vaccines.

The determinants of immunodominance are multifactorial. They include how efficiently an epitope is generated and presented: proteasomal processing, transport into the endoplasmic reticulum by TAP, peptide-MHC binding affinity and complex stability, and the abundance and accessibility of the antigen. T cell precursor frequency and TCR repertoire shape which epitopes are recognized, as do regulatory networks and co-stimulation. The immunological environment, tissue site, and infection dynamics also alter the hierarchy.

Consequences and applications: Immunodominance can drive protection when dominant epitopes are protective, but it can impede breadth and allow immune escape if pathogens mutate these epitopes. Individual HLA/MHC polymorphism creates variation in dominance hierarchies across people. In vaccines and immunotherapies, designers seek to modulate immunodominance to broaden coverage, for example by including multiple epitopes, mosaic antigens, altering antigen processing, or using adjuvants that shift hierarchy.

Limitations: Immunodominance is context-dependent and does not always predict protective outcomes; subdominant epitopes may be crucial for protection or cross-reactivity.