Class I MHC is stabilized against thermal denaturation by physiological concentrations of NaCl

Class I MHC molecules are ternary complexes composed of an allotype specifi c heavy chain, a noncovalently associated protein beta(2)-microglobulin (be ta(2)m), and a peptide. The complexes are assembled in the endoplasmic reti culum by a complex series of chaperones and peptide-loading mechanisms. In the absence of beta(2)m or peptide, very little class I heavy chain is tran sported to the surface of the cell. Complexes that do not contain all three parts of the protein are not made productively in vivo and not at all in v itro. The ability of the complex to withstand thermal denaturation in vitro has been shown to be related to the binding affinity of the peptide. Parad oxically, some low-affinity peptide complexes denature at or below human ba sal body temperatures in vitro but are effective biological agents in vivo, Here we show that these complexes are stabilized against thermal denaturat ion by physiological cosolvents and maximally stabilized by 150 mM NaCl. Wh ile the degree of stabilization by 150 mM NaCl is greatest for low-affinity peptide/MHC complexes, the mechanism of stabilization is independent of pe ptide sequence. This effect is hypothesized to occur by multiple mechanisms including increasing the affinity of beta(2)m for the complex and charge s creening,.