Methods to activate or block the HLA-E/Qa-1 restricted CD8+ T cell regulatory pathway to treat immunological disease

Methods are provided for inhibiting or enhancing down-regulation of an antigen-activated HLA-E + T cell by an HLA-E-restricted CD8 + T cell comprising contacting the HLA-E + T cell and CD8 + T cell with an agent which inhibits or enhances, respectively, binding between (i) T cell receptor (TCR) on the surface of the CD8 + T cell and (ii) a self peptide presented by HLA-E on the surface of the HLA-E + T cell, thereby inhibiting or enhancing, respectively, down-regulation of the antigen-activated HLA-E + T cell. Compositions comprising agents which inhibit or enhance/activate, respectively, binding between (i) T cell receptor (TCR) on the surface of a CD8 + T cell and (ii) a self peptide presented by HLA-E on the surface of a HLA-E + T cell, and assays for identifying such agents, are provided.