MHC-INDEPENDENT PRESENTATION OF MYCOBACTERIA TO HUMAN GAMMA-DELTA-T-CELLS

The majority of human peripheral gammadelta T cells express antigen receptors using the V(gamma)9 and V(delta)2 gene products. Cells of this subset have been previously shown to uniformly recognize mycobacteria regardless of their V-(D)-J junctional sequences in an MHC-unrestricted manner. This reactivity superficially resembles activation of alphabeta cells by bacterial superantigens, which are thought to be presented by monomorphic regions of MHC class II molecules. It is not known whether presentation of the mycobacterial antigen to V(gamma)9/V(delta)2 T cells is also mediated by class II MHC molecules. In order to examine the similarity between presentation of bacterial superantigens to alphabeta T cells and the presentation of mycobacteria to gammadelta T cells we have studied the role of class II MHC molecules in presentation of the mycobacterial antigen AP-MT to V(gamma)9/V(delta)2 clones. Activation of gammadelta T cells by AP-MT required direct contact with antigen presenting cells, indicating that an interaction with cell surface molecules on antigen presenting cells is required. Class II MHC molecules were neither sufficient nor necessary for effective presentation of AP-MT to the gammadelta T cells, as transfectants expressing class II MHC molecules were unable to present, whereas cell lines lacking expression of MHC class II molecules could present this mycobacterial antigen. Unlike presentation of staphylococcal enterotoxins to alphabeta T cells, which could be mediated by class II transfectants and was significantly augmented by co-expression of intercellular adhesion molecule (ICAM)-1, presentation of AP-MT to gammadelta T cells could not be enhanced by co-expression of class II and ICAM-1 molecules. Based on these results and our previous observation that presentation of AP-MT is independent of class I MHC molecules, we conclude that presentation of mycobacteria to human V(gamma)9/V(delta)2 cells can be mediated by non-MHC cell surface molecules. These results indicate that despite apparent similarities, recognition of mycobacteria by V(gamma)9/V(delta)2 cells and activation of alphabeta T cells by bacterial superantigens involve distinct presentation mechanisms.