Human ICOSLG ELISA Matched Antibody Pair

T cell activation plays a central role in immune response and in the maintenance of self-tolerance. We analyzed the evolutionary history of T cell regulatory molecules. Nine genes involved in triggering T cell activation or in regulating the ensuing response evolved adaptively in mammals. Several positively selected sites overlap with positions interacting with the binding partner or with cellular components. Population genetic analysis in humans revealed a complex scenario of local (FASLG, CD40LG, HAVCR2) and worldwide (FAS, ICOSLG) adaptation and H. sapiens-to-Neandertal gene flow (gene transfer between populations). Disease variants in these genes are preferential targets of pathogen-driven selection, and a Crohn's disease risk polymorphism targeted by bacterial-driven selection modulates the expression of ICOSLG in response to a bacterial superantigen. Therefore, we used evolutionary information to generate experimentally testable hypotheses concerning the function of specific genetic variants and indicate that adaptation to infection underlies the maintenance of autoimmune risk alleles.

In this study, we sought to determine whether the expression of inducible co-stimulator ligand (ICOSLG) on mouse hematologic neoplasm cells influences cytotoxicity. Using flow cytometry, we examined the expression of ICOSLG in mouse hematologic neoplasm cell lines for the first time and used FBL3/A20 as targets to study. Effectors and targets were incubated at effector: target (E: T) ratios ranging from 5:1 to 50:1 for 10 h. Enzyme-linked immunosorbent assay was used to assess the expression of cytokines associated with type 2 T helper cells. We found that FBL3, A20 and P388 cells expressed ICOSLG. At E:T ratios ranging from 20:1 to 30:1, the cytotoxic activity of alloreactive T cells was significantly increased when ICOSLG was blocked (p < 0.05). We also found that ICOSLG blockade was associated with decreased expression of interleukin 4 and interleukin 10. Our results indicate that ICOSLG blockade may enhance cytotoxity in allogeneic mixed lymphocyte-hematologic neoplasm cell reactions.