Innate Natural Antibodies. Primary Roles Indicated by Specific Epitopes

Two members of a unique class of natural antibodies have been identified in all of a large cohort of sera from clinically normal humans of broad age distribution. By means of a series of 10–12 mer peptides the epitope for each of those antibodies was characterized with regard to amino acid identity and conformation. Similar epitope specificity was revealed for the IgM isotopes of cord blood and early post natal sera and for IgM and IgG of adult sera, suggesting that the class of natural antibodies represented by the two identified in this study includes those genomically coded for at their effector level of maturation in the B cells of the neonate. Assay of series of specimens from each of four clinically normal adults revealed that those two natural antibodies are present at relatively constant titer, unique to each individual, over four to five and a half year periods. Those observations imply that the primary function of that class of natural antibodies may be related to maintenance of homeostasis and the molecular identity of each of the two epitopes suggests a role, for each, as monitor or control in intracellular traffic. The previous identification of those epitopes in a conserved protein of HIV also provides support for the proposition that a secondary function of natural antibodies, arising from fortuitous coincidence of the identity of the epitopes, may be that of early defense against infectious invaders.