CTL immunodominance The mechanisms of immunodominance are very poorly understood. What determines
cytotoxic T lymphocyte (CTL) immunodominance can be a number of factors, many of which are debated. Of these, one in particular focuses on the timing of CTL clonal expansion. The dominant CTLs that arise were activated sooner so therefore proliferate faster than subdominant CTLs that were activated later, thus resulting in a greater number of CTLs for that immunodominant epitope. This can be in concordance with an additional theory which states that immunodominance may be dependent on the affinity of the
T-cell receptor (TCR) to the immunodominant epitope. That is, T cells with a TCR that has high affinity for its antigen are most likely to be immunodominant. High affinity of the peptide to the TCR contributes to the T cell’s survival and proliferation, allowing for more clonal selection of the immunodominant T cells over the subdominant T cells. Immunodominant T cells also curtail subdominant T cells by outcompeting them for cytokine sources from antigen-presenting cells. This leads to a greater expansion of the T cells that recognize a high affinity epitope and is favoured since these cells are likely to clear the infection much more quickly and effectively than their subdominant counterparts. It is important to note, however, that immunodominance is a relative term. If subdominant epitopes are introduced without the dominant epitope, the immune response will be focused to that subdominant epitope. Meanwhile, if the dominant epitope is introduced with the subdominant epitope, the immune response will be directed against the dominant epitope while silencing the response against the subdominant epitope.
Antibody immunodominance The mechanism of immunodominance in B cell activation focuses on the affinity of epitope binding to the
B-cell receptor (BCR). If an epitope binds very strongly to a B cell BCR, it will then subsequently bind with high affinity to the resultant antibodies produced by that B cell upon activation. These antibodies then out-compete the BCR for the epitope, and thus that B cell lineage will be unavailable for subsequent stimulation. On the opposite end of the scale where BCRs have low affinity for the epitopes, these B cells are outcompeted for stimulation by B cells with BCRs that have higher affinities for their respective epitopes. Insufficient T cell stimulation by these B cells also leads to suppression of these B cells by the T cells. The immunodominant epitope will be a BCR that has a particular ‘goldilocks’ amount of affinity for its epitope determined by equilibrium binding affinity. This leads to initial IgM response directed at the strongly binding epitope, and the subsequent IgG response focused on the immunodominant epitope. That is, those within the ‘goldilocks zone’ for affinity will be available for subsequent T helper stimulation, allowing for class switching,
affinity maturation and thus, resulting in immunodominance to that particular epitope. ==Implications==