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The University of Southampton
Chemistry

Research project: Attard: Theoretical Studies Of Biological Processes: Modelling Of The Class I Immune Response Pathway

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The Class I-restricted antigen processing and presentation pathway provides a sophisticated surveillance mechanism aimed at detecting viral infection in cells.

One of the most intriguing aspects of this type of immune response is that discrimination between self and non-self is based on the recognition by T lymphocytes (via the T cell receptor) of short oligopeptides (predominantly nonamers) presented on the surfaces of cells in association with the products of the major histocompatibility complex I (MHC I). These oligopeptides are derived from intracellular proteins, and in effect the population of MHC/peptide complexes present at the cell surface at any moment in time represents a snapshot of the cytosolic protein population. We have used experimental data on MHC/peptide populations on cell surfaces to show that the MHC/peptide distribution is highly biased and can be modelled by the Kohlrausch-Williams-Watts (KWW) equation with a characteristic exponent g=0.37±0.02. This means that the population is dominated by a only few peptide species, the precise nature of which fluctuates with time, reflecting the metabolic status of the cell. On the basis of the relatively small number of numerically dominant, but temporally fluctuating, MHC/peptide species a T cell bearing an appropriate receptor can distinguish between those peptides that are derived from self and those that are derived from non-self (e.g. viruses). Our current research is aimed at developing a model of extra-thymic self/non-self discimination which is based on MHC/peptide distributions governed by the KWW equation. We are employing Information Theory to analyse the information content of these population distributions and are constructing a simulation of the discrimination process.

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