ANTIGEN PRESENTATION BY DENDRITIC CELLS FOCUSES T-CELL RESPONSES AGAINST IMMUNODOMINANT PEPTIDES - STUDIES IN THE HEN EGG-WHITE LYSOZYME (HEL) MODEL

T lymphocyte responses to a protein Ag are restricted to a limited num ber 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 t he H-2(d) haplotype, hen egg-white lysozyme (HEL)-specific T lymphocyt es react with I-E-d-restricted peptides derived from a single immunodo minant (ID) region (HEL 103-117), Moreover, we have recently found tha t another region of HEL (HEL 7-31) binds to I-A(d) molecules and is ef ficiently processed and presented by splenocytes. HEL7-31 is as tolero genic as the ID region in HEL transgenic mice. The present report demo nstrates 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 a ll BALB/c mice. We show that normal and lymphoma B cells present effic iently HEL regions 103-117 and 7-31, whereas dendritic cells favor the ID region only, These results suggest that dendritic cells play a maj or role in the focusing of the immune response against a few antigenic determinants, while B lymphocytes may diversify the T cell response b y presenting a more heterogeneous set of peptide-MHC complexes.