Persistent Antigens Hypothesis: The Human Leukocyte Antigen (HLA) Connection

Abstract

HLA genes play a critical role in immune protection from foreign antigens including viruses, bacteria, and parasites1. Located in the Major Histocompatibility Complex (MHC) of chromosome 6, HLA genes code for glycoproteins that exist on the surface of most cells in order to facilitate immune surveillance and initiate an immune response to eliminate foreign antigens. There are two main classes of HLA (Class I and Class II) that support the elimination of cytosolic or extracellular foreign antigens through cell destruction and antibody production, respectively. HLA genes have evolved to be the most highly polymorphic in the human genome, thereby maximizing species resistance to foreign antigens and promoting survival. Nonetheless, successful elimination of foreign antigens is predicated on a match between one’s HLA and epitopes derived from foreign antigen proteins. Each person has a limited repertoire of HLA proteins inherited in a Mendelian fashion for each class. Fortunately, each HLA protein can match with various epitopes and, since everyone has one or two alleles at each of the classical loci (Class I HLA-A, B, and C and Class II HLA-DP, DQ, and DR), a large number of antigens can be effectively eliminated.