  The T cell arm of the adaptive immune system provides the host protection
against unknown pathogens by discriminating between host and foreign material.
This discriminatory capability is achieved by the creation of a repertoire of
cells each carrying a T cell receptor (TCR) specific to non-self antigens
displayed as peptides bound to the major histocompatibility complex (pMHC). The
understanding of the dynamics of the adaptive immune system at a repertoire
level is complex, due to both the nuanced interaction of a TCR-pMHC pair and to
the number of different possible TCR-pMHC pairings, making computationally
exact solutions currently unfeasible. To gain some insight into this problem,
we study an affinity-based model for TCR-pMHC binding in which a crystal
structure is used to generate a distance-based contact map that weights the
pairwise amino acid interactions. We find that the TCR-pMHC binding energy
distribution strongly depends both on the number of contacts and the repeat
structure allowed by the topology of the contact map of choice; this in turn
influences T cell recognition probability during negative selection, with
higher variances leading to higher survival probabilities. In addition, we
quantify the degree to which neoantigens with mutations in sites with higher
contacts are recognized at a higher rate.
