"MHC CLASS I ANTIGEN PROCESSING MACHINERY REGULATES MHC CLASS II ASSOCIATED ANTIGENIC PEPTIDE REPERTOIRE"

MHC class II-restricted CD4 T helper cells regulate the generation and function of effector and memory CD8 T lymphocyte (CTL) responses. It is generally assumed that peptides derived from extracellular proteins (e.g., those that negotiate the endosomal and lysosomal vesicles) are presented by MHC class II molecules. However, current evidence suggests that peptides presented by MHC class II molecules can be derived from cytosolic proteins as well. In an effort to understand how peptides derived from cytosolic proteins are processed for presentation by MHC class II molecules, I discovered that the cytosolic proteasome and the endoplasmic reticulum-associated amino-peptidase (ERAAP) severely restrict the pool of antigenic peptides presented by MHC class II molecules. Thus, I propose that MHC class I processing pathway regulates the repertoire of antigenic peptides presented by MHC class II molecules, thereby regulating CD4 T cell immunodominance and CTL responses to pathogens and transplantation antigens.