The peptidic self model: a hypothesis on the molecular nature of the immunological self

We propose that peptide presentation by class I and class II antigens of the major histocompatibility complex is a general phenomenon. Peptides derived from the breakdown of most or all cellular proteins and able to associate with class I or class II antigens would be continuously presented at the surface of cells. The set of peptides exposed at the surface of somatic cells, called in short the "somatic self", would be under permanent immune surveillance. A protein would be recognized as "foreign" primarily because at least one of its presented peptides does not belong to the somatic self. We speculate that the same peptide presentation process operates within cells of the immune system, and we discuss some of the possible implications. Since this "peptidic self" model imposes strong constraints on primary structures, we have undertaken a preliminary analysis of several peptides with known immunological properties. We show that they all contain patterns of amino acids not found in the protein sequence data banks available at present for the relevant organisms, in agreement with the starting hypothesis.