Single chain MHC complexes and uses thereof

DETAILED DESCRIPTION The present invention relates to novel complexes of major histocompability complex (MHC) molecules (class I or II), e.
g.
, empty single chain MHC class II complexes, loaded single chain MHC class II complexes, and single chain MHC class II peptide fusion complexes and the uses of such MHC complexes.
We have now discovered that single chain MHC class complexes without a covalently linked presenting peptide (i.
e.
an empty MHC complex) can be loaded by contacting a presenting peptide to the complex so that the presenting peptide non-covalently binds to the peptide binding groove of the complex.
Generally, the presenting peptide will non-covalently bind to the peptide binding groove of the empty MHC complex via stable hydrogen bonding.
The single chain MHC class complexes of the present invention, particularly single chain MHC class II complexes, are surprisingly stable and are useful in a variety of applications.
For example, loaded single chain MHC class II complexes or single chain MHC class II peptide fusion complexes can be used to modulate various immune system responses in a mammal, e.
g.
, T cell apoptosis, T cell anergy, T cell cytokine release, immunosuppression and induction of T cells.
Empty MHC molecules, particularly empty single chain MHC class II molecules, are useful in, e.
g.
, in vitro screens for detecting peptides that modulate the activity of T cells, including peptides which are T cell receptor antagonists and partial agonists.
We previously disclosed highly useful MHC class I and class II peptide fusion molecules in unpublished PCT Application No.
PCT/US95/09816, filed Jul.
31, 1995 (sometimes referred to herein as said "PCT Application") as well as pending U.
S.
application Ser.
No.
08/382,454, filed Feb.
1, 1995.
The MHC fusion complexes comprise a presenting peptide covalently linked (i.
e.
fused) to the MHC molecule.
The PCT Application No.
PCT/US95/09816 and said U.
S.
application Ser.
No.
08/382,454 are herein incorporated by reference in its entirety