Cutting Edge: Chemical Dominance Does Not Relate to Immunodominance: Studies of the CD4+ T Cell Response to a Model Antigen

We have quantitated the major families of peptides from hen egg lysozyme (HEL) presented by MHC class II I-A(k) molecules. One striking feature is that the four epitopes are presented at levels that differ by as much as 200- to 300-fold. In these studies, we describe the CD4(+) T cell response to each epitope after immunization with several doses of hen egg lysozyme protein. Although fewer T cells were generated at lower doses, the surprising finding was the responses to all four peptides were maintained. The relative number of T cell clones to each of the four epitopes was influenced to a very limited degree by their levels of presentation at the lowest dose. In conclusion, under strong stimulatory conditions, there is not a direct relationship between levels of peptide presentation and the T cell responses.