MOLECULES encoded by the human GDI locus on chromosome 1 (ref. 33) are recognized by selected CD4⁻8⁻ T-cell clones expressing either αβ or γδ T-cell antigen receptors^1,2. The known structural resemblance of GDI molecules to antigen-presenting molecules encoded by major histocompatibility complex (MHG) genes on human chromosome 6 (refs 3, 4, 34, 35), suggested that GDI may represent a family of antigen-presenting molecules separate from those encoded in the MHC^1,5,6. Here we report that the proliferative and cytotoxic responses of human CD4⁻8⁻αβTCR⁺ T cells specific for Mycobacterium tuberculosis can be restricted by GDlb, one of the four identified protein products of the GDI locus. The responses of these T cells to M. tuberculosis seemed not to involve MHG encoded molecules, but were absolutely dependent on the expression of GDlb by the antigen-presenting cell and involved an antigen processing requirement similar to that seen in MHC class Il-restricted antigen presentation. These results provide, to our knowledge, the first direct evidence for the proposed antigen-presenting function of GDI molecules and suggest that the GDI family plays a role in cell-mediated immunity to microbial pathogens.