N-glycosylation of HIV-gp120 may constrain recognition by T lymphocytes.

Botarelli, Patrizia; Houlden, Bronwyn A.; Haigwood, Nancy L.; Servis, Catherine; Montagna, Daniela; Abrignani, Sergio

doi:10.4049/jimmunol.147.9.3128

Cited by 69 publications

(1 citation statement)

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“…In particular, we believe HLA-associated adaptations to Env glycoproteins were especially limited because Env is primarily targeted by antibodies, not CD8 þ T cells. Furthermore, the amount of glycosylation present on gp120 and gp41 prohibits efficient presentation of Env antigens to T cells [30].…”

Section: Discussionmentioning

confidence: 99%

HLA-associated preadaptation in HIV Vif is associated with higher set point viral load and faster CD4+ decline in Zambian transmission pairs

Connolly

Carlson

Schaefer

et al. 2021

Aids

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Objective(s): We investigated the relationship between human leukocyte antigen (HLA)-associated preadaptation for the entire subtype C HIV-1 proteome of the transmitted founder virus and subsequent HIV-1 disease progression in a cohort of heterosexual linked transmission pairs in Zambia.Design: An adaptation model was used to calculate an adaptation score for each virus-HLA combination in order to quantify the degree of preadaptation of the transmitted virus to the linked recipient's HLA alleles. These scores were then assessed for their relationship to viral load and longitudinal CD4 þ decline in the recipient.Methods: Viral RNA was extracted from the plasma of the donor partner and the linked recipient near the time of transmission, as well as longitudinally from the linked recipient. Viral adaptation scores were calculated for each individual and each protein in the subtype C HIV-1 proteome. Results:The majority of HLA-associated sites were located in Gag, Pol and Nef; however, proportional to protein length, the accessory and regulatory proteins contained a relatively high proportion of HLA-associated sites. Over the course of infection, HLA-mediated immune adaptation increased for all proteins except Vpu and gp120. Preadaptation was positively associated with higher early set point viral load and faster CD4 þ decline. When examined by protein, preadaptation in Pol and Vif were statistically significantly associated with these markers of disease progression. Conclusion:Adaptation in Pol had the greatest impact on viral control. Despite containing a large proportion of HLA-associated sites, Vif was the only regulatory or accessory protein for which preadaptation significantly correlated with disease progression.

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Section: Discussionmentioning

confidence: 99%

HLA-associated preadaptation in HIV Vif is associated with higher set point viral load and faster CD4+ decline in Zambian transmission pairs

Connolly

Carlson

Schaefer

et al. 2021

Aids

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Glycobiology of AIDS

Feizi

Ernst

Hart

et al. 2000

Carbohydrates in Chemistry and Biology

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Role of flanking variable sequences in antigenicity of consensus regions of HIV gp120 for recognition by specific human T helper clones

et al. 1993

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Human T helper cells can discriminate among strain variants of HIV gp120 because of T cell clones recognizing non-conserved regions, as demonstrated with T cells from HIV-infected individuals and vaccinated volunteers and with primary T cell lines and clones obtained by in vitro immunization. To obtain a better definition of cross-reactions among T cell determinants within HIV gp120 variants, we used a panel of analog peptides within residues 236-251 from the BRU, MN, SF2 and RF strain sequences to induce primary human T cell lines and clones. Different patterns of response were obtained using each of the analog peptides, although they all share the consensus sequence 246-251. Clones recognizing this sequence were generated by priming with the BRU and RF analog peptides, but not with the SF2 analog peptide. SF2 did not induce any 242-245-specific clones, but only T cells recognizing the 236-240 sequence. A preferential response to residues 236-240 was obtained by priming with the BRU and SF2 peptides, but not with the MN and RF peptides. These results suggest that although the analog peptides exhibit a high degree of homology and share a consensus of the C-terminal sequence (246-251), the T cell response to the conserved sequence 246-251 is controlled by flanking sequences. Therefore the presence of a shared sequence per se does not imply in vitro expansion of clones with that fine specificity, even though such clones are available within the naive repertoire and can be triggered by an analog peptide.

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N-glycosylation of HIV-gp120 may constrain recognition by T lymphocytes.

Cited by 69 publications

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HLA-associated preadaptation in HIV Vif is associated with higher set point viral load and faster CD4+ decline in Zambian transmission pairs

HLA-associated preadaptation in HIV Vif is associated with higher set point viral load and faster CD4+ decline in Zambian transmission pairs

Glycobiology of AIDS

Role of flanking variable sequences in antigenicity of consensus regions of HIV gp120 for recognition by specific human T helper clones

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