Alanine-substituted peptide ligands differ greatly in their ability to activate autoreactive T-cell subsets specific...

Alanine-substituted peptide ligands (APLs) have the potential to reduce or block autoreactive T-cell activation. Most previous investigations aimed at either identification of the amino acid residue within a peptide ligand that is critical for T-cell activation or characterization of inhibitory APLs have analyzed the effects of APLs on one, or a limited number, of T-cell lines. In this study, we compared the effects of a panel of peptides on the proliferative and activation responses of one T-cell line as well as the effects of one peptide on the responses of a panel of T-cell lines. This study reveals that the T cells that comprise the T-cell population that responds to a specific peptide are heterogeneous in that an APL may fail to induce a response in some of these T cells although it is capable of inducing a response in the others. Moreover, APLs can induce T-cell activation, in terms of production of IL-2 and/or TNF-alpha, in the absence of appreciable cell proliferation. Indeed, despite being poor stimulators in proliferation assays, most APLs readily induce production of TNF-alpha. Our results demonstrate that the net outcome of APL treatment in vivo represents the sum of diverse effects, which may not be revealed completely by limited and randomly chosen in vitro assays.