INFLUENCE OF CD26 AND INTEGRINS ON THE ANTIGEN SENSITIVITY OF HUMAN-MEMORY T-CELLS

The antigen sensitivity of class II MHC-restricted human CD4 T-cell cl ones is demonstrated to increase gradually with time after restimulati on. This is manifested in a requirement of less antigen in culture, as well as decreased numbers of peptide-MHC complexes per APC for T-cell activation, and in an increased resistance to inhibition by class II MHC blockade. The increase in antigen sensitivity is accompanied by in creased cell-surface expression of CD26, LFA-1, and VLA-1, whereas the expression of TCR and a series of other cell-surface molecules remain s unchanged. Using appropriate monoclonal antibodies, we have shown th at CD26 and LFA-1 contribute directly to the increased antigen sensiti vity of ''late-stage'' T-cell clones. The late-memory T-cell phenotype established in this study is shown to occur also among T cells activa ted in vivo. We suggest that increasing the antigen sensitivity via an tigen-nonspecific molecules is a physiologic mechanism for maintaining T-cell memory in face of decreasing antigen concentration, and for en suring preferential activation of memory T cells upon repeated encount er with antigen.