MYPPPY variants of CTL A4 and uses thereof

DETAILED DESCRIPTION OF THE INVENTION Definition As used in this application, the following words or phrases have the meanings specified.
As used herein "blocking B7 interaction" means to interfere with the binding of the B7 antigens to their ligands such as CD28 and/or CTLA4 thereby obstructing T cell and B cell interaction.
As used herein a "B7-binding molecule" means any molecule which will bind any one or both of the B7 antigens.
As used herein a "molecule reactive with the CD80 antigen" means any molecule which will recognize and bind CD80.
As used herein a "molecule reactive with the CD86 antigen" means any molecule which will recognize and bind CD86.
As used herein a "non-CTLA4 molecule" means any molecule which can be attached or joined to the extracellular domain of CTLA4 and does not interfere with CTLA4 binding to its target.
These molecules include a polypeptide tag, an immunoglobulin (Ig) tail, a biologically or chemically active protein such as the papillomavirus E7 gene product, melanoma-associated antigen p97, and HIV env protein or a sequence of amino acids which renders soluble and active the extracellular portion of CTLA4 or mutagenized forms thereof.
In order that the invention herein described may be more fully understood, the following description is set forth.
Compositions of the Invention The invention provides CTLA4 mutant molecules reactive with the CD80 antigen, wherein in the extracellular domain of CTLA4 the first tyrosine in the amino acid motif MYPPPY (SEQ ID NO 11) is replaced by an amino acid other than tyrosine.
CTLA4 mutant molecules may be embodied in many forms.
The only limitation being that it retain its ability to bind CD80.
In one embodiment of the invention, the CTLA4 mutant molecule is a functional, soluble CTLA4 mutant molecule.
The extracellular domain of CTLA4 is an example of a soluble CTLA4 mutant molecule.
In one example, the soluble CTLA4 mutant molecule binds the CD80 antigen but does not bind the CD86 antigen.
In a further embodiment of the invention, the soluble CTLA4 mutant molecule has the extracellular domain of mutagenized CTLA4 joined to a non-CTLA4 molecule (also referred to as CTLA4 mutant fusion proteins) such as a polypeptide tag