HLA-B*57-associated polymorphisms in EC, and their relationship with Nef function. Panel A: Two-dimensional map of B*57-associated polymorphisms identified in an exploratory analysis of the EC cohort using phylogenetically-corrected approaches with p<0.05 . “Nonadapted” forms (those less likely to be observed in the presence of B*57 at a specific location) are shown above the Nef protein in blue; “adapted” forms (those enriched among B*57-expressing persons) are shown below the Nef protein in red. Due to limited statistical power and other reasons, both nonadapted and adapted forms are not always identified at a given position. Boxed codons indicate those where the amino acid varied in B*57 EC; the remainder were either expressed in 100% of B*57 EC (adapted forms 3G and 19F) or 0% of B*57 EC (nonadapted forms 105Q, 178G, 198M). In subsequent analyses, Nef sequences from B*57-expressing persons were counted as harboring a B*57-associated polymorphism at a given site if that site expressed anything other than the nonadapted form, or the adapted form if no nonadapted form was identified. Panel B: The locations of the nine EC-specific B*57-associated polymorphisms are indicated in green on the structure model of the Nef protein (composite crystal structure kindly provided by Art F. Y. Poon, ) Panels C- G: Correlations between the number of B*57-associated polymorphisms in Nef sequences from B*57-expressing EC, and five Nef functions evaluated. Statistical analyses were done using Spearman’s correlation.