The vertebrate immune system includes numerous proteins involved in the recognition and elimination of parasitic organisms. In vertebrates, the most important system for eliminating intracellular parasites (such as viruses) involves presentation of parasite-derived peptides by class I major histocompatibility complex (MHC) molecules to cytotoxic T cells (CD8+TL). The general goals of this research are to understand the origin and evolution of key molecular components of the vertebrate immune system and to understand the evolution of molecular adaptations in parasitic organisms that evade recognition and elimination by the host's immune system. The methods used in this research involve statistical analysis of published DNA sequence data, of which a large amount is now available both for immune system genes and for genes of major human pathogens (particularly viruses). The purposes of these analyses are as follows: (1) to test the hypothesis that the recognition systems of vertebrate immunity have given rise to natural selection favoring amino acid sequence diversity in parasite protein regions that are targets for immune recognition, while parasites have correspondingly selection for variation in host immune system molecules; (2) to test the hypothesis that epitopes presented by the host MHC to CD8+TL are subject to conflicting selection pressures, including both selection to evade immune recognition and selection to conserve sequence patterns important for viral fitness; (3) to reconstruct patterns of recombination in the evolution of pathogenic viruses and bacteria; and (4) to use phylogenetic analyses of key immune system families, along with information regarding their expression and interactions, in order to reconstruct the evolutionary process whereby members of multi-gene families playing key roles in the immune system have become functionally differentiated. By increasing our understanding of how genetic variation enables pathogens to evade recognition and elimination by the human immune system, this research will provide basic knowledge useful in designing public health strategies to counteract important human pathogens such as human immunodeficiency virus 1 (HIV-1) and hepatitis C virus. In addition, by increasing our understanding of the population diversity and evolutionary history of human immune system genes, this research will enhance our knowledge of human immune function in health and disease. ? ? ?
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