TAT-BASED IMMUNOMODULATORY COMPOSITIONS AND METHODS FOR THEIR DISCOVERY AND USE

1 . A method for identifying new immunomodulatory chemical entities (NICE) comprising:

a. reacting a candidate NICE with a Tat SH3 binding domain wherein said Tat SH3 binding domain is bound to a solid phase to identify candidate NICE that bind to said Tat SH3;

b. identifying said candidate NICE bound to said Tat SH3;

c. adding said identified candidate NICE to a culture of purified peripheral blood monocytes;

d. adding Tat having an SH3 binding domain to said peripheral blood monocytes and candidate NICE to form a test culture;

e. incubating said test culture to allow said monocytes to differentiate into dendritic cells (DC) or regulatory macrophages (AReg);

f. removing said differentiated cells from said test culture and determining the presence or absence of DCs or AReg.

2 . The method according to claim 1 wherein said Tat SH3 binding domain in step (a) is selected from the group consisting of native immunosuppressive human immunodeficiency virus (HIV) Tat, simian lentivirus Tat, long-term non-responder Tat, randomly mutated HIV Tat and site-specific mutated HIV Tat.

3 . The method according to claim 1 further comprising the step of injecting confirmed immunostimulatory NICE from step (f) of claim 1 into an immunosuppressed mouse wherein said immunosuppression results from the presence of an endogenous SH3 binding domain.

4 . The method according to claim 2 wherein the said immunosuppressive mouse is a hairless (hr) mouse.

5 . A method according to claim 1 further comprising the step of injecting a tolerogenic NICE from step (f) of claim 1 into a mouse and further challenging said mouse with an antigen wherein said tolerance results from the pre-treatment with tolerogenic NICE.