Identification of conserved @entity1522 in murine B7-1IgV domain critical for @entity17796 / XXXX :B7 interaction by site-directed mutagenesis: a novel structural model of the binding site.

@entity1522 @entity70712 @entity5 @entity8271 @entity17796 @entity70711 @entity10867 @entity70710
The B7: @entity10867 / @entity17796 interaction plays a major role in T cell responses. Immune intervention targeted at this interaction has demonstrated a vast potential in enhancing @entity5 immunity and blocking autoimmunity and transplant rejection. However, the structural basis for this interaction is unclear. While we and others have performed site-directed mutagenesis to define @entity1522 involved in binding @entity10867 and @entity17796 , these residues are localized in different regions, and it is unlikely for all of them to be directly involved. In addition, the effect of the mutations on the overall conformation of B7 has not been systematically evaluated. In this study, we have carried out site-directed mutagenesis to define the @entity1522 within @entity8271 IgV-like domain which participate B7: @entity10867 / @entity17796 interaction. Four anti- @entity8271 mAbs that recognize three independent antigenic epitopes on @entity8271 were used to monitor the effect of mutations on the overall conformation of @entity8271 . Of the five mutations in the IgV domain that we have produced, @entity70710 appears to interfere with cell surface expression and/or overall conformation of @entity8271 . while four others do not significantly affect the overall conformation and cell surface expression of @entity8271 . Among them, @entity70711 and Y91 > A eliminated @entity8271 binding to both CD28Ig and CTLA4Ig; our previously reported mutants @entity70712 and W88 > A selectively affect the @entity8271 binding to either CD28Ig or CTLA4Ig. Structural modeling of @entity8271 based on the structure of immunoglobulin revealed that these four and other previously identified critical @entity1522 in both IgV- and IgC-like domains can form a localized structure.
