Inhibition of T-Cell Activation by a CEACAM1 (CD66a) Peptide

Carcinoembryonic antigen family (CEACAM) members are widely expressed, and depending on the tissue, capable of regulating diverse functions, including tumor promotion, tumor suppression, angiogenesis, neutrophil activation, and T-cell activation. CEACAM1, a member of the carcinoembryonic antigen family, is expressed on human T-cells and is recognized by CD66a mAb. CD66a mAb binding to the T-cell surface inhibits T-cell activation. To identify active sites on CEACAM1, molecular modeling was performed using IgG and CD4 as models, and 28 peptides of 14 amino acids in length were synthesized that were predicted to be present at loops and turns between beta-sheets. The peptides were tested for their ability to alter T-cell activation by anti-CD3 and IL-2. One peptide from the internal domain inhibited T-cell activation. Scrambled versions of this peptide had no effect on T-cell activation. The data suggest that a peptide motif from the internal domain of CEACAM1 is involved in the interaction of CEACAM1 with other ligands and can alter signal transduction in T-cells. This peptide may serve as a template for the development of structurally related compounds that can regulate T-cell activation.