CLASS II major histocompatibility complex (MHC) molecules are heterodimeric cell surface glycoproteins which bind and present immunogenic peptides to T lymphocytes. Such peptides are normally derived from protein antigens internalized and proteolytically degraded by the antigen-presenting cell¹. Class I MHC molecules also bind immunogenic peptides, but these are derived from proteins synthesized within the target cell². Whereas class I molecules seem to bind peptides in the endoplasmic reticulum^3–5, class II molecules are thought to bind peptides late in transport. Intracellular class II molecules associate in the endoplasmic reticulum with a third glycoprotein, the invariant (I) chain, which is proteolytically removed before cell surface expression of the αβ class II heterodimer^6,7. It has been suggested that the I chain prevents peptides from associating with class II molecules early in transport⁸. Preventing such binding until the class II molecules enter an endosomal compartment could maintain the functional dichotomy between class I and class II MHC molecules. We have examined the ability of I chain-associated HLA-DR5 moleculesto bind a well characterized influenza haemagglutinin-derived peptide (HAp). The results show that whereas mature HLA-DR αβ dimers effectively bind this peptide, the I chain-associated form does not.