The N-terminal region of tapasin is required to stabilize the MHC class I loading complex

Tapasin mediates the binding of MHC class I molecules to the transporter as sociated with antigen processing (TAP). Deletion mutants of tapasin were us ed to examine the effect of tapasin on interactions within the MHC class I complex. Binding to TAP is mediated by the C-terminal region of tapasin. Mi chaelis-Menten analysis of peptide transport shows that this interaction is sufficient to increase TAP levels without significantly affecting the intr insic translocation rate. Weak interactions exist between MHC class I molec ules and TAP in the absence of tapasin, and between free heavy chains and T AP-tapasin complexes in the absence of beta 2-microglobulin. The N-terminal 50 residues of tapasin constitute the key element which converts the sum o f these weak interactions into a stable complex.