Effects of end groups on the stimulatory capacity of minimal length T cell determinant peptides

We studied the effect of end groups on the capacity of two closely related peptides to stimulate a human T cell clone. Using multipin peptide synthesis technology, we generated solution phase peptides with six combinations of end groups for each sequence. The end modifications examined were amino-terminal acetylation, carboxy-terminal methylamidation or the addition of a dipeptide containing a diketopiperazine ring. The response to the less stimulatory of the two peptide sequences was significantly increased by acetylation of the amino-terminus, a finding which was consistent at different peptide doses. Amino-terminal acetylation was found to be more significant in affecting responses than any of the carboxy-terminal modifications tested. The use of peptides with a diketopiperazine ring structure at the carboxy-terminus did not interfere with presentation and recognition of peptides and may enhance the effectiveness of peptides for T cell epitope scanning.