Within the human population, many alleles exist for each of the 6 HLA types. Because each person has a pair of each HLA type (codominantly expressed), or 1 haplotype, an APC expresses pairs of MHC molecules. Thus, except for identical twins, only rarely will all potential haplotypes match between 2 individuals.
Allelic diversity provides protection through population-wide immunity. Each HLA haplotype covers a theoretical set of antigens against which an individual can respond. The presence of many different HLA alleles within a population should thus ensure that the collective adaptive immune system can respond to a wide range of potential pathogens. The converse also holds true: some individuals may be at increased risk for immunologic diseases because of either an aberrantly strong immune response to a benign pathogen or an autoimmune disease arising from inappropriate recognition of host peptides in the context of a particular HLA being recognized as foreign. See Clinical Example 4-1.
Clinical detection and classification of different alleles
Determination of HLA type has evolved from prior antisera reactions to molecular techniques that determine the nucleic acid sequence of MHC alleles. Molecules of HLA are composed of 2 chains: the α chain and β chain for class II, and the α chain and the β2-microglobulin chain for class I. Genotyping specifies the chain, major genetic type, and specific minor molecular variant subtype. For example, genotype DRB1*0408 refers to the HLA-DR4 molecule β chain with the “–08” minor variant subtype. Haplotypes now recognized as a single group will continue to be subdivided into new categories or new subtypes as research progresses.
Excerpted from BCSC 2020-2021 series: Section 9 - Uveitis and Ocular Inflammation. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.