To more carefully determine how a peptide antigen interacts with the antigen-presenting cell (APC), we have begun an analysis of the fate of APC-associated peptide antigens. These studies have shown that a stable cell-bound form of APC-associated peptide exists, which is a complex of the peptide with surface membrane structures (peak A). In the experiments described here, we have begun to examine the chemical mechanism of this peak A complex formation. By modifying either the carboxyl terminal or amino terminal group of the octapeptide antigen angiotensin II we have established that the terminal carboxyl group, but not the terminal amino group, was critical for forming the peak A complex with APC membrane structures. In addition, blocking the carboxyl but not the amino terminal dramatically reduced the antigenicity of the peptide for AII-immune T cell in vitro proliferation. These results show that the carboxyl terminal of AII is essential for both peak A formation and antigenicity, and suggest that peak A is critical for antigen presentation to T cells.