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The lower epitope yields might reflect a combination of a greater adaptive potential of this region in HIV C, differences between African and white HLA alleles, a bias in the database toward HIV B epitopes, and/or the longer history of the HIV epidemic in Africa. We next fitted the same model to epitope yields from the constitutive proteasomal digestions and found similar patterns (t test, p?= 0.39�C0.95) (Table S2). As a result of the HLA-mediated adaptation of HIV to proteasomal preferences, the CD8 epitopes presented by rare HLA variants are produced in greater quantities than those presented either by common variants or by a combination of rare and common variants and might therefore be more likely to prime (Faroudi et?al., 2003) and/or be recognized by CTL (Purbhoo et?al., [http://www.selleckchem.com/products/AP24534.html Ponatinib research buy] 2004). Collectively, our data provide compelling evidence that these clinically important p24 HIV Gag regions [http://en.wikipedia.org/wiki/Oxalosuccinic_acid Oxalosuccinic acid] adapt to proteasomal preferences at the population level in response to selection pressures that are imposed by all epitope-restricting HLA class I variants in an HLA frequency-dependent manner. To examine how TAP transport and ERAP trimming preferences might affect the predicted epitope presentation and recognition at the cell surface, we tested the subset of epitope precursors with the protective IW9, KF11, KI, or TW10 motifs (Figure?2A). To induce a CTL response, the epitope-precursor fragments must first be transported by TAP into the ER, and, because TAP transport rate is determined by binding, not translocation (Gubler et?al., 1998), we measured [http://www.selleckchem.com/products/mi-773-sar405838.html MI-773 clinical trial] the normalized TAP affinities of the precursors (Figure?2B). TAP binding affinity was sequence but not length specific, given that TAP sometimes bound long epitope precursors (>16 amino acids) better than shorter peptides containing only parts of the longer sequence (e.g., AF19 versus VF14 and VF15, Figure?2B). Overall, most precursors were transported well, especially those produced in the greatest abundance (affinity