The c.305del3 inIL-2gene in Homonoidea theoretically affects IL-2/IL-2Rα interaction as well as lymphocyte homeostasis

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Abstract

Interleukin-2 (IL-2) is a well-known monomeric T-cell growth factor that is produced primarily by activated CD4+ T cells following exposure to antigen. IL-2 structural analysis among primates showed a few polymorphisms as well as a 3-nucleotide deletion (c.305del3) in Hominoidea superfamily including Homo sapiens. On the other hand, the interaction of IL-2 with its alpha subunit of the receptor (IL-2Rα) is the first step for assembly of the whole IL-2R and considered as a species-specific phase. Four models of human IL-2, IL-2Rα, and their ancestral forms were made and were used for molecular dynamics (MD) simulation. Subsequently, the final structures were docked to each other and finally, the complexes were used for MD simulation. Our results showed that the above mentioned deletion led to weaker interaction of human IL-2 to its receptor relative to ancestral IL-2. Association study of lymphocyte counts, as an indicator of IL-2 function, in 78 primate species with or without this deletion showed significant association of this deletion with their overall lymphocyte counts (P < .01). Therefore, it can be suggested that p.81delThr in IL-2 in Hominides superfamily interfered with interaction of IL-2 and IL-2Rα and led to overall decrease in lymphocyte counts in this superfamily of primates in comparison with other primates.

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