Association of the human invariant chain with H‐2 Db class I molecules

Abstract

We describe two proteins of 24 kDa and 33 kDa (p24 and p33) which associate with H‐2 K^b and H‐2 D^b molecules, respectively, in human cells transfected with H‐2 K^b and H‐2 D^b genes. This association is particularly clear in the mutant cell line T2, in which association of endogenous peptide with newly synthesized class I molecules may not occur (V. Cerundolo et al., Nature 1990. 345: 449). We show that p33 is the 33‐kDa form of the human invariant chain which is resident in the endoplasmic reticulum of T2 cells (P. Cresswell, Cold Spring Harbor Symp. Quant. Biol. 1989. LIV: 309). The stability of the invariant chain H‐2 D^b complex is critically dependent upon occupation of the class I binding site by peptide ligand. In the absence of peptide, the complex is stable at 4°C whereas following exposure to peptide, the invariant chain dissociates rapidly from H‐2 D^b molecules (half‐life of 30 min at 4°C). Although the interaction between the human invariant chain and murine H‐2 D^b is unlikely to have any functional significance, the peptide‐induced dissociation of the invariant chain is consistent with a conformational change in H‐2 D^b on peptide binding.