IMMUNOLOGICAL EFFECTS OF AN ARGININE SIDE-CHAIN CONTAMINATING SYNTHETICALLY PREPARED PEPTIDES

The side chain, 4-methoxy-2,3,6-trimethylbenzenesulphonyl (Mtr), is a protective group coupled to arginine to mask the omega-nitrogen, in or der to protect the guanidino function during peptide synthesis by the 9-fluorenylmethoxycarbonyl (Fmoc) procedure (Walker, 1994). This group is removed at the completion of peptide synthesis; however, the cleav age process can be incomplete. We have found that animals injected wit h a mixed population of pure, i.e. unmodified, and Mtr-containing MBP peptides have an immunodominant humoral response to the Mtr-bearing pe ptide. This response is dependent on the characteristics of the MBP pe ptide involved. For two MBP peptides, the Mtr-containing peptide had i ncreased binding to antibody over pure peptide. For two other peptides , only the Mtr-containing peptide bound antibody while the unmodified peptide did not. In a separate system involving a polyclonal response to an unrelated peptide from beta(2)-microglobulin (beta(2) m), the do minance of the Mtr group was also evident. These results provide furth er evidence that a small side chain on a single amino acid in a peptid e can markedly alter the immunogenicity and antigenicity of that pepti de for antibody reactivity. This evidence emphasizes the need for a cr itical awareness of each component of peptide synthesis and its potent ial to alter the immunoreactivity of the final product.