Antigen presentation by dendritic cells focuses T cell responses against immunodominant peptides: studies in the hen egg-white lysozyme (HEL) model

Abstract

T lymphocyte responses to a protein Ag are restricted to a limited number of determinants and not to all peptides capable of binding to MHC class II molecules. This focusing of the immune response is defined as immunodominance and has been observed with numerous protein Ags. In the H-2d haplotype, hen egg-white lysozyme (HEL)-specific T lymphocytes react with I-Ed-restricted peptides derived from a single immunodominant (ID) region (HEL 103-117). Moreover, we have recently found that another region of HEL (HEL 7-31) binds to I-Ad molecules and is efficiently processed and presented by splenocytes. HEL7-31 is as tolerogenic as the ID region in HEL transgenic mice. The present report demonstrates that the subdominance of the HEL 7-31 region is not due to a defect in the T cell repertoire, since specific TCRs can be found in all BALB/c mice. We show that normal and lymphoma B cells present efficiently HEL regions 103-117 and 7-31, whereas dendritic cells favor the ID region only. These results suggest that dendritic cells play a major role in the focusing of the immune response against a few antigenic determinants, while B lymphocytes may diversify the T cell response by presenting a more heterogeneous set of peptide-MHC complexes.