Specificity of Mycobacteria/Self-Reactive γδ Cells

Abstract

The γδ T cell receptor (TCR), although structurally quite similar to the αβ TCR, may differ in terms of the ligand recognized, MHC restriction, and the immunological role of the cells that express it. αβ TCR-expressing cells are biased to recognize allogeneic MHC molecules, presumably because the allogeneic molecules three-dimensionally resemble self MHC molecules containing a bound foreign peptide. This implies that if γδ TCRs recognize the same kind of ligand, they should produce a similar frequency of alloreactivity. Although when cultured under conditions that select for cells that respond to allogeneic MHC molecules, γδ cells can be isolated with alloantigenic specificities (Bluestone et al., 1988; Matis et al., 1989; Rivas et al., 1989; Spits et al., 1990), γδ cells isolated under conditions not involving such selection usually show no alloreactivity (Haregewoin et al., 1989; Holoshitz et al., 1989; Modlin et al., 1989; O’Brien et al., 1989). Moreover, alloreactivity by γδ cells often shows a broad cross-reactivity uncommon among αβ T cells (Bluestone et al., 1988; Matis et al., 1989). Also, in many cases, nonclassical MHC or MHC-like molecules such as mouse TL (Bonneville et al., 1989; Dent et al., 1990), mouse Qa-1 (Vidovic et al., 1989), and human CD1 (Porcelli et al., 1989), have been implicated as γδ TCR ligands, although classical MHC class I (Bluestone et al., 1988; Rivas et al., 1989; Spits et al., 1990) and II (Bluestone et al., 1988; Kozbor et al., 1989) molecules have been reported as well. Thus, while molecules that serve as αβ TCR ligands can be recognized by at least some γδ TCRs, the recognition usually seems to be less specific in terms of polymorphic determinants, and frequently involves molecules that are rarely found as αβ TCR ligands. These observations may indicate that the antigens recognized by γδ T cells also tend to be of a different sort than those recognized by αβ T cells.