Immunological cross-reactivity of antibodies to a synthetic undecapeptide analogous to the amino terminal segment of carcinoembryonic antigen, with the intact protein and with human sera.

Abstract

A peptide corresponding to the 11 amino acid residues of the NHT-terminal portion in the sequence of carcinoembryonic antigen(CEA) has been synthesized by the solid phase technique. The synthetic CEA(1-11) peptide was attached by means of a water-soluble carbodiimide reagent to multichain poly(DL-alanine) as well as to bovine serum albumin. Both macromolecular conjugates provoked in rabbit anti-CEA(1-11) peptide antibodies. The specificity of this immunological system and the crossreactivity between the peptide and intact CEA were investigated-by two methods-passive hemagglutination and modified bacteriophage inactivation. Hemagglutination experiments showed that not only anti-CEA(1-11) sera, but also anti-CEA sera, agglutinated CEA(1-11)coated sheep erythrocytes, and both these reactions were inhibited with CEA(1-11) peptide. In experiments with the chemically modified bacteriophage technique CEA(1-11)coated phage was efficiently inactivated with antisera against the CEA(1-11) conjugates, and the inactivation reaction could be totally inhibited with the free peptide. The semipure CEA, but not the pure protein, could also inhibit the phage inactivation, even thoug less efficiently.On the basis of the above results, sera of some cancer patients were tested for their capacity, to inhibit the inactivation of CEA(1-11)coated phage by means of anti-CEA(1-11) antiserum. The results indicate that sera from a large proportion of patients with adenocarcinomas of the digestive tract, pancreas, and breast are capable of inhibiting the above inactivation, whereas most normal sera do not inhibit.

Antiviral response elicited by a completely synthetic antigen with built-in adjuvanticity.

“…For example, antibodies provoked by a synthetic peptide comprising the "loop" region of the enzyme lysozyme attached to a synthetic carrier were reactive with native lysozyme (5). Similarly, antibodies elicited by a synthetic antigen containing the NH2-terminal region of the carcinoembryonic antigen of the colon were reactive with the intact protein, and capable of detecting carcinoembryonic antigens in sera of cancer patients (6). We have also shown that this approach could be used for provoking an antiviral response.…”

From Proteins and Protein Models to Their Use in Immunology and Immunotherapy

“…We first synthesized a peptide from the amino terminus of the carcinoembryonic antigen of the colon; this showed a weak cross-reaction with the intact antigen (55). The first study related to viruses was the synthesis of a peptide from the envelope of the MS2 bacteriophage (34).…”