Different roles of D‐amino acids in immune phenomena

Peptides and polypeptides either fully or partially built of D‐amino acids interest researchers because of their advantages over all L peptides and polypeptides. In exploiting these characteristics, one should realize that the resulting molecules are nonetheless not inert, but rather may induce a unique immune response, which is hardly cross‐reactive with the L‐enantiomer. Moreover, cross‐reaction between the L‐and the D‐sequences is limited also at the T cell level, probably due to different sterical conformations of the MHC‐antigen‐T cell receptor complexes formed. Polypeptides built exclusively of D‐amino acids lead to antibody formation only at a relatively low concentration, otherwise they provoke immunological paralysis. The specificity of the immune response toward peptides containing D‐amino acid residues is exquisite, and often D‐amino acids play a dominant role in defining the specificity. Polypeptides composed exclusively of D‐amino acids are thymus‐independent antigens. Nevertheless, it is possible to prepare against them highly specific T cell hybridomas. In future plans for synthetic vaccines against infectious or autoimmune diseases, the inclusion of D‐amino acids may be an advantage in terms of both specificity and efficacy, the latter because of longer persistence in an undigested form because they resist enzymatic degradation.—Sela, M., Zisman, E. Different roles of D‐amino acids in immune phenomena. FASEB J. 11, 449–456 (1997)