Mammalian non-classical major histocompatibility complex I and its receptors: Important contexts of gene, evolution, and immunity.

The evolutionary conserved, less‑polymorphic, nonclassical major histocompatibility complex (MHC) class I molecules: Qa‑1 and its human homologue human leukocyte antigen‑E (HLA‑E) along with HLA‑F, G and H cross‑talk with the T‑cell receptors and also interact with natural killer T‑cells and other lymphocytes. Moreover, these nonclassical MHC molecules are known to interact with CD94/NKG2 heterodimeric receptors to induce immune responses and immune regulations. This dual role of Qa‑1/ HLA‑E in terms of innate and adaptive immunity makes them more interesting. This review highlights the new updates of the mammalian nonclassical MHC‑I molecules in terms of their gene organization, evolutionary perspective and their role in immunity.

GITR expression on T-cell receptor-stimulated human CD8+ T cell in a JNK-dependent pathway.

Glucocorticoid-induced tumor necrosis factor receptor (TNFR) (GITR) family-related gene is a member of the TNFR super family. GITR works as one of the immunoregulatory molecule on CD4+ regulatory T cells and has an important role on cell survival or cell death in CD4+ T cells. Little is known about the expression of GITR on human CD8+ T cells on antigen-specific and non-specific activation. Here, we report that expression of GITR on human CD8+ T cells on T-cell receptor (TCR) (anti-CD3)-mediated stimulation is dependent on the JNK pathway. The activation of CD8+ T cells was measured by the expression of IL-2 receptor-α (CD25), GITR and by IFN-γ production upon re-stimulation with anti-CD3 antibody. We studied the signaling pathway of such inducible expression of GITR on CD8+ T cells. We found that a known JNK-specific inhibitor, SP600125, significantly down-regulates GITR expression on anti-CD3 antibody-mediated activated CD8+ T cells by limiting JNK phosphorylation. Subsequently, after stimulation of the CD8+ cells, we tested for the production of IFN-γ by the activated cells following restimulation with the same stimulus. It appears that the expression of GITR on activated human CD8+ T cells might also be regulated through the JNK pathway when the activation is through TCR stimulation. Therefore, GITR serves as an activation marker on activated CD8+ cells and interference with JNK phosphorylation, partially or completely, by varying the doses of SP600125 might have implications in CD8+ cytotoxic T cell response in translational research.