HLA-Cw*03-Restricted CD8⁺T-Cell Responses Targeting the HIV-1 Gag Major Homology Region Drive Virus Immune Escape and Fitness Constraints Compensated for by Intracodon Variation

Human Leukocyte Antigen Variants B*44 and B*57 Are Consistently Favorable during Two Distinct Phases of Primary HIV-1 Infection in Sub-Saharan Africans with Several Viral Subtypes

“…In most studies, a quantitative measure of VL is used without reference to estimated date of infection (EDI), under the assumption that patients are seldom observed during acute-phase (peak) infection and that the early chronic-phase (set-point) VL is usually stable for years in patients with no apparent manifestations of immunodeficiency. Factors known or suspected to influence VL range from viral mutations (changes in replication fitness or switches in coreceptor tropism) (15,28,39,72) to host genes that govern innate and adaptive immune responses (54,75,81,83,84,86).…”

“…In most studies, a quantitative measure of VL is used without reference to estimated date of infection (EDI), under the assumption that patients are seldom observed during acute-phase (peak) infection and that the early chronic-phase (set-point) VL is usually stable for years in patients with no apparent manifestations of immunodeficiency. Factors known or suspected to influence VL range from viral mutations (changes in replication fitness or switches in coreceptor tropism) (15,28,39,72) to host genes that govern innate and adaptive immune responses (54,75,81,83,84,86).Within the human nuclear genome, human leukocyte antigen (HLA) class I genes are the most convincing (and universally applicable) quantitative trait loci for HIV-1 viremia (14,16,17,66). However, the individual HLA alleles, haplotypes, and supertypes with reported impacts on HIV-1 VL are not always clear because their distribution and patterns of linkage disequilibrium often differ from one population to another (7,53,63).…”

Sequence variations in HIV-1 p24 Gag-derived epitopes can alter binding of KIR2DL2 to HLA-C*03

“…We furthermore observed a highly significant but moderate correlation between percentile rank scores of all 222 OLPs and our HLA-C stabilization assay values (Spearmans r -value 0.24, p- value < 0.0001, figure 1C). Three of the seven identified HLA-C*03:04 binding peptides had also previously been described in the Los Alamos database to contain HLA-C*03:04-restricted CTL epitopes; OLP11 (Gag140-152 and Gag145-152) [35, 36], OLP34 (Gag167-175) [37] and OLP163 (Gag295-304) [38-42] (table 1). However, two other previously described HLA-C*03-restricted CTL epitopes, TLRAEQATQD (Gag303-312) [43] and KALGPAATL (Gag335-343) [37], were not identified using our stabilization assay, probably due to sequence differences between the described epitope and the epitope used in our assay (TLRAEQASQE versus TLRAEQATQD and KALGPAATLE versus KALGPAATL) [37, 43].…”

Pyrosequencing Reveals Restricted Patterns of CD8 + T Cell Escape-Associated Compensatory Mutations in Simian Immunodeficiency Virus

“…These epitopes are found in regions of the virus that are conserved due to structural or functional constraints (8,15,20). However, compensatory mutations found near a subset of these epitopes enable intraepitope variation and maintenance of viral replication (4,7,10,21,22,26).…”

“…Determination of an optimal set of HIV-derived CD8 ϩ T cell antigens and deployment of these antigens in an appropriate vector are major goals of HIV vaccine research. Thus, understanding how host cellular immune responses drive viral sequence evolution is crucial for rational vaccine design.Certain major histocompatibility complex (MHC) class Ibound epitopes found in individuals infected with HIV or simian immunodeficiency virus (SIV) show a limited capacity for variation, with escape mutations often only occurring late (if at all) in chronic infection (8,15,20). These epitopes are found in regions of the virus that are conserved due to structural or functional constraints (8,15,20).…”