Andrej Košmrlj: Indications of host genetics for T cell development and HIV control

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  Indications of host genetics for T cell development and HIV control  

  Andrej Košmrlj,  Physics Department, MIT, Cambridge, ZDA

The adaptive immune system mounts pathogen-specific responses to a diverse and evolving world of microbes, for which specificity cannot be pre-programmed. T cells orchestrate adaptive immune responses. T cell surface is covered with receptors (TCRs) that recognize short peptides, which are derived from pathogenic proteins and are displayed on the surface of cells that harbor pathogens.  Remarkably, TCR recognition of foreign peptides is both specific and degenerate.  If a TCR recognizes a particular peptide, most point mutations to the peptide abrogate recognition (specificity), but a TCR can recognize several different foreign peptides (degeneracy). We present a statistical mechanical model of T cell development in the thymus gland that sheds light on how developmental processes select T cells that can recognize pathogens in a specific, yet degenerate, fashion. Our model allows identification of a new contributing factor to why people with certain genes are more likely to control HIV infection without therapy. The latter ideas have been tested against human clinical data.