Am. Little et al., DISSOCIATION OF BETA-2-MICROGLOBULIN FROM HLA CLASS-I HEAVY-CHAINS CORRELATES WITH ACQUISITION OF EPITOPES IN THE CYTOPLASMIC TAIL, The Journal of immunology, 154(10), 1995, pp. 5205-5215
A rabbit antiserum ''ABR2'' was raised against a peptide with sequence
identity to 10 amino acids of the cytoplasmic tail of HLA class I hea
vy chains. Western blotting and immunoprecipitation analyses demonstra
te that ABR2 reacts with HLA class I heavy chains. The antiserum react
s poorly with beta 2-microglobulin (beta(2)-m)-associated heavy chains
and reacts strongly with free heavy chains. ABR2 reacts with immature
heavy chains from the endoplasmic reticulum that have yet to bind bet
a(2)-m and mature heavy chains that have dissociated from beta(2)-m at
the plasma membrane. Comparison with HC10, a mAb that recognizes an e
pitope defined by polymorphism at residue 62 of the alpha 1 helix of f
ree HLA class I heavy chains, shows that ABR2 reacts with overlapping
populations of free heavy chains (for those allotypes that react with
both Abs), but it also identifies populations that bind to one Ab and
not the other. ABR2 induces dissociation of beta 2-m from HLA-B38 mole
cules expressed by the human B cell line ''TEM,'' a phenomenon not det
ected with other allotypes or with the same allotype in a different ce
ll line. This study shows that association of beta 2-m with the extrac
ellular domains of HLA class I heavy chains can cause a change in the
cytoplasmic tail that prevents binding of Abs present in the ABR2 anti
serum. Similar findings have been made for mouse H-2 class I molecules
, which suggests that this is a general property of class I MHC molecu
les.