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  • Novel Genes Involved in T Cell AnergyStudies originally performed in 1998 by Drs. Fathman and Bloom of Stanford's School of Medicine yielded partial information of several genes involved in T cell anergy. Now, they have identified five anergy genes, three of which are novel and may be of interest for promoting immunosuppression.Differential display was used to identify several novel genes that are uniquely expressed or upregulated in the state of T cell anergy. Although some of these genes were previously identified, murine and, ultimately, human homologs must be identified in several instances. In multiple cases, the newly identified anergy genes do not have counterparts in the database. These genes were identified by utilizing the technique of differential display and comparing, in three different lanes, mRNA run out as cDNA utilizing commercial differential display kits corresponding to a resting murine T cell clone and its activated counterpart, as well as the anergic counterpart. The activated cells were given both signals for activation including antigen in MHC association plus B7 through the use of L cells transfected for appropriate expression. The anergy T cells were presented antigen in the appropriate MHC, in the absence of co-stimulation, utilizing an L cell that had not been transfected for expression of B7.By using two in-vivo "anergy induction" systems, an anergic phenotype was developed. mRNA expression in these anergic cloned T cells was compared to mRNA expression in T cells under resting or activating conditions. Via comparison between the anergic and active cells, five candidate "anergy genes" were identified:- Four have partial or significant homology to known genes - One bears no DNA sequence homology to any known gene - Three of the genes are novel and are new potential targets for immunoregulation - Confidential information is available on the identity of these genes and their roles in regulating T cell activation