SPECIES-SPECIFIC DIFFERENCES IN CHAPERONE INTERACTION OF HUMAN AND MOUSE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I MOLECULES

Previous studies have shown that immature mouse class I molecules tran siently associate with a resident endoplasmic reticulum protein of 88 kD that has been proposed to act as a chaperone for class I assembly. Subsequently this protein was demonstrated to be identical to calnexin and to associate with immature forms of the T cell receptor complex, immunoglobulin, and human class I HLA heavy chains. In this paper we d efine further the interaction of human class I HLA heavy chains with c haperone proteins and find key differencess with the complexes observe d in the mouse system. First, calnexin and immunoglobulin binding prot ein (BiP) both associate with immature HLA class I heavy chains. The t wo chaperones are not found within the same molecular complex, suggest ing that calnexin and BiP do not interact simultaneously with the same HLA class I heavy chain. Second, only free HLA class I heavy chains, and not beta(2)-microglobulin (beta(2)m)-associated heavy chains are f ound associated with the chaperones. Indeed, addition of free beta(2)m in vitro induces dissociation of chaperone-class I HLA heavy chain co mplexes. The kinetics for dissociation of the class I HLA heavy chain- chaperone complexes and for formation of the class I HLA heavy chain-b eta(2)m complex display a reciprocity that suggests the interactions w ith chaperone and beta(2)m are mutually exclusive. Mouse class I heavy chains expressed in human cells exhibit the mouse pattern of interact ion with human chaperones and human Pam and not the human pattern, sho wing the difference in behavior is purely a function of the class I he avy chain sequence.