TRUNCATION OF THE CLASS-II BETA-CHAIN CYTOPLASMIC DOMAIN INFLUENCES THE LEVEL OF CLASS-II INVARIANT CHAIN-DERIVED PEPTIDE COMPLEXES

Previous studies have established that antigen presenting cells (APC) expressing major histocompatibility complex class II beta chains with truncated cytoplasmic domains are impaired in their capacity to activa te T cells. While it had been widely accepted that this impairment is due to a defect in class II cytoplasmic domain-dependent signal transd uction, we recently generated transgenic mice expressing only truncate d class II beta chains, and functional analyses of APC from these mice revealed signaling-independent defects in antigen presentation, Here, we demonstrate that T cells primed on such transgenic APC respond bet ter to stimulation by APC expressing truncated beta chains than by wil d-type APC. This finding suggests that APC expressing truncated class II beta chains are not inherently defective in their antigen presentin g capacity but, rather, may differ from wild-type APC in the peptide a ntigens that they present, Indeed, analysis of the peptides bound to c lass II molecules isolated from normal and transgenic spleen cells rev ealed clear differences, Most notably, the level of class II-associate d invariant chain-derived peptides (CLIP) is significantly reduced in cells expressing only truncated beta chains, Prior studies have establ ished that CLIP and antigenic peptides compete for binding to class II molecules. Thus, our results suggest that the cytoplasmic domain of t he class II beta chain affects antigen presentation by influencing the level of CLIP/class II complexes.