Gg. Capps et al., IN-VIVO DIMERIC ASSOCIATION OF CLASS-I MHC HEAVY-CHAINS - POSSIBLE RELATIONSHIP TO CLASS-I MHC HEAVY CHAIN-BETA(2)-MICROGLOBULIN DISSOCIATION, The Journal of immunology, 151(1), 1993, pp. 159-169
Class I MHC molecules have been thought to occur in vivo both as class
I MHC heavy chain-beta2-m heterodimers, which are or are not associat
ed with antigenic peptide, and as free class I MHC heavy chains. Class
I MHC molecules are now found also to occur in another type of struct
ure: a heavy chain-heavy chain dimer. Biochemical studies show that he
avy chain dimers are disulfide-linked via a conserved cytoplasmic doma
in cysteine. H-2L(d), H-2D(b), and H-2D(d) class I dimers fail to reac
t with certain alpha1 and alpha2 domain-specific antibodies. Furthermo
re, although beta2-m-specific antibodies coprecipitate class I MHC hea
vy chains, they do not coprecipitate class I MHC heavy chain dimers. P
ulse-chase studies show that heavy chain dimer formation occurs at dif
ferent points in the biosynthesis of class I MHC molecules in beta2-m and beta2-m- Cells: in beta2-m+ cells, heavy chain dimers form after
the class I molecules have traversed the medial Golgi cisternae, where
as in beta2-m- cells they form immediately. Culturing of beta2-m+ cell
s with exogenous beta2-m prevents the formation of H-2L(d)/D(b) heavy
chain dimers. We conclude that dimer formation occurs as a consequence
of loss or unavailability of beta2-m. Class I MHC heavy chain dimeriz
ation may provide a mechanism for removal of immunologically dysfuncti
onal molecules.