Protective HLA alleles are associated with reduced LPS levels in acute HIV infection with implications for immune activation and pathogenesis
Fig 6
Individuals with CD4-protective HLA class I alleles more efficiently target conserved regions of Gag.
(A) A graphical depiction of a generalized linear model showing the relative association between the presence of CD4-protective HLA class I alleles with IFNγ ELISpot responses to Gag PTE peptide pools from cryopreserved PBMCs collected a median of 45 days post infection. A correction factor for transmitted Gag sequence similarity to the PTE peptide pools was added as a covariate. The distance between horizontal lines represent the difference in means between individuals with (light blue, n = 6) and without (gray, n = 27) protective HLA class I alleles whereas the direction of the lines represents regression between the two continuous variables: Gag sequence similarity to peptide pools (x-axis) and IFNγ ELISpot responses reported as spot forming units per million PBMCs (y-axis). (B) Cryopreserved PBMCs collected at one-year post infection (median 339 days post infection) were interrogated with peptide pools containing 300 clade C consensus 10-mer PTE Gag peptides, with subsequent deconvolution to identify single peptide responses. The number of individual Gag peptide responses for individuals with (blue bar, n = 6) and without (gray bar, n = 12) CD4-protective HLA class I alleles are depicted. (C) A graphical depiction of a generalized linear model showing the relative association between the presence of CD4-protective HLA class I alleles with IFNγ ELISpot responses to Gag HIVconsv peptides [51] from cryopreserved PBMCs collected a median of 45 days post infection. A correction factor for transmitted Gag sequence similarity to the 3 Gag regions covered by the 31 HIVconsv Gag peptides was added as a covariate. The distance between horizontal lines represent the difference in means between individuals with (light blue, n = 6) and without (gray, n = 27) protective HLA class I alleles whereas the direction of the lines represents regression between the two continuous variables: Gag sequence similarity to HIVconsv Gag peptides (x-axis) and IFNγ ELISpot responses reported as spot forming units per million PBMCs (y-axis).