The Power of the MHC

 HLA MHC Complex on

 Human Chromosome 6

Infectious diseases threaten us and our animals on a daily basis. However, inside the human body on chromosome 6, there is a group of genes that is essential for your protection and health. A May 2013 paper by Kubinak et al. examined viral evolution in the context of the major histocompatibility complex (MHC). The MHC is one of the most gene-dense regions in the vertebrate genome (Kubinak et al. 2013). Although in humans, it is only approximately 3600 kb in length, it contains roughly 224 genes, 40% of which have been found to have immunological functions (Garrigan 2003). Therefore, despite making up only 0.1% of the genome, it contains a disproportionate number of genes associated with immunity. It is evident that the MHC is crucial to the immune system.

Infectious and autoimmune diseases have been correlated to polymorphisms within the MHC. Polymorphisms are defined as different alleles of a gene existing in a population. The high levels of polymorphisms in the MHC are suggested to be due to co-evolution between host genotypes and pathogens. In other words, the “pathogen bad guys” evolve to avoid detection by the “good guys” in our bodies. The “good guys” respond though a process by which MHC genes encode cell surface proteins which bind and present peptide antigens (in the form of peptide MHC complexes) to T cells. A T cell mediated immune response (“good guys” spring into action) is then triggered if the antigen is recognized as foreign. Specifically, pathogen adaptation and virulence evolution seem to be locked in a battle with polymorphic antigen-presenting MHC genes for control of the health of the human body. It is primarily the interaction effect between the virus genotype and the host genotype that dictates variation in viral fitness and virulence, not the individual effects of virus genotype or host genotype (Table 1). This leads to specialization between a particular pathogen and host genotype.