Av. Chervonsky et al., SUBTLE CONFORMATIONAL-CHANGES INDUCED IN MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II MOLECULES BY BINDING PEPTIDES, Proceedings of the National Academy of Sciences of the United Statesof America, 95(17), 1998, pp. 10094-10099
Intracellular trafficking of major histocompatibility complex (MHC) cl
ass II molecules is characterized by passage through specialized endoc
ytic compartment(s) where antigenic peptides replace invariant chain f
ragments in the presence of the DM protein. These changes are accompan
ied by structural transitions of the MHC molecules that can be visuali
zed by formation of compact SDS-resistant dimers, by changes in bindin
g of mAbs, and by changes in T cell responses. We have observed that a
mAb (25-9-17) that is capable of staining I-Ab on the surface of norm
al B cells failed to interact with I-Ab complexes with a peptide deriv
ed from the E-alpha chain of the I-E molecule but bound a similar cova
lent complex of I-Ab with the class IT binding fragment (class LI-asso
ciated invariant chain peptides) of the invariant chain. Moreover, 25-
9-17 blocked activation of several I-Ab-reactive T cell hybridomas but
failed to block others, suggesting that numerous I-Ab-peptide complex
es acquire the 25-9-17(+) or 25-9-17(-) conformation. Alloreactive T c
ells were also able to discriminate peptide-dependent variants of MHC
class II molecules. Thus, peptides impose subtle structural transition
s upon MHC class II molecules that affect T cell recognition and may t
hus be critical for T cell selection and autiommunity.