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

The majority of human peripheral gammadelta T cells express antigen re ceptors 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-unrestrict ed manner. This reactivity superficially resembles activation of alpha beta cells by bacterial superantigens, which are thought to be present ed by monomorphic regions of MHC class II molecules. It is not known w hether 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 exam ine 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 presentat ion 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 su rface molecules on antigen presenting cells is required. Class II MHC molecules were neither sufficient nor necessary for effective presenta tion of AP-MT to the gammadelta T cells, as transfectants expressing c lass II MHC molecules were unable to present, whereas cell lines lacki ng expression of MHC class II molecules could present this mycobacteri al antigen. Unlike presentation of staphylococcal enterotoxins to alph abeta T cells, which could be mediated by class II transfectants and w as significantly augmented by co-expression of intercellular adhesion molecule (ICAM)-1, presentation of AP-MT to gammadelta T cells could n ot be enhanced by co-expression of class II and ICAM-1 molecules. Base d on these results and our previous observation that presentation of A P-MT is independent of class I MHC molecules, we conclude that present ation of mycobacteria to human V(gamma)9/V(delta)2 cells can be mediat ed by non-MHC cell surface molecules. These results indicate that desp ite apparent similarities, recognition of mycobacteria by V(gamma)9/V( delta)2 cells and activation of alphabeta T cells by bacterial superan tigens involve distinct presentation mechanisms.