Qa-1 restriction of CD8+ suppressor T cells

Abstract

There is increasing evidence that the immune response can be inhibited by several T cell subsets, including NK T cells, CD25+CD4+ T cells, and a subpopulation of CD8+ T cells. Animal model studies of multiple sclerosis have suggested an important role for suppressor CD8+ T cells in protection against disease recurrence and exacerbation. The molecular lynchpin of CD8+ suppressive activity is the murine MHC molecule Qa-1, termed HLA-E in humans. Here we summarize findings from work on Qa-1 that have begun to delineate suppressor CD8+ T cells and their mechanisms of action in the context of self tolerance and autoimmune disease.

Figure 1

Engagement of Qa-1 by the TCR and by CD94/NKG2A. (A) Presentation of Qa-1–bacterial GroEL peptide by a DC following Salmonella infection to CD8⁺ T cells, where the receptor is a TCR, leads to CTL responses. (B) Presentation of Qa-1–self peptides by activated CD4⁺ T cells to CD8⁺ T cells, where the receptor is a TCR, leads to the development of Qa-1–restricted suppressor CD8⁺ T cells. (C) Engagement of CD94/NKG2A receptors on CD8⁺ T cells with a DC can inhibit either TCR-mediated CTL responses specific for Qa-1–foreign peptide ligands and/or TCR-mediated suppressive responses specific for Qa-1–self peptide ligands. This NKG2A-dependent interaction may regulate expression of suppressor or cytotoxic CD8⁺ T cells through inhibition of cellular activation or diminished AICD.