Structures of Three HIV-1 HLA-B*5703-Peptide Complexes and Identification of Related HLAs Potentially Associated with Long-Term Nonprogression

Stewart‐Jones, Guillaume; Gillespie, Geraldine M.; Overton, Ian M.; Kaul, Rupert; Roché, Philippe; McMichael, Andrew J.; Rowland‐Jones, Sarah; Jones, E.Y.

doi:10.4049/jimmunol.175.4.2459

Cited by 70 publications

(77 citation statements)

References 56 publications

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“…These particular alleles have been strongly associated with slow progression to disease and thus theoretically would exert a strong selective pressure on the virus (53 (52,56,61,81). The positively selected mutation in clade A1, A163G at the P2 anchor position of the KAF11 and KAF8 epitopes, is highly correlated with patients expressing HLA-B*5703 (P ϭ 3.21 ϫ 10 Ϫ8 ).…”

Section: Fig 1 Comparison Of Individual Residue Entropies Between Tmentioning

confidence: 78%

An Integrative Bioinformatic Approach for Studying Escape Mutations in Human Immunodeficiency Virus Type 1gagin the Pumwani Sex Worker Cohort

Peters¹,

Mendoza

Capiña

et al. 2008

J Virol

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Human immunodeficiency virus type 1 (HIV-1) is able to evade the host cytotoxic T-lymphocyte (CTL)response through a variety of escape avenues. Epitopes that are presented to CTLs are first processed in the presenting cell in several steps, including proteasomal cleavage, transport to the endoplasmic reticulum, binding by the HLA molecule, and finally presentation to the T-cell receptor. An understanding of the potential of the virus to escape CTL responses can aid in designing an effective vaccine. To investigate such a potential, we analyzed HIV-1 gag from 468 HIV-1-positive Kenyan women by using several bioinformatic approaches that allowed the identification of positively selected amino acids in the HIV-1 gag region and study of the effects that these mutations could have on the various stages of antigen processing. Correlations between positively selected residues and mean CD4 counts also allowed study of the effect of mutation on HIV disease progression. A number of mutations that could create or destroy proteasomal cleavage sites or reduce binding affinity of the transport antigen processing protein, effectively hindering epitope presentation, were identified. Many mutations correlated with the presence of specific HLA alleles and with lower or higher CD4 counts. For instance, the mutation V190I in subtype A1-infected individuals is associated with HLA-B*5802 (P ‫؍‬ 4.73 ؋ 10 ؊4 ), a rapid-progression allele according to other studies, and also to a decreased mean CD4 count (P ‫؍‬ 0.019). Thus, V190I is a possible HLA escape mutant. This method classifies many positively selected mutations across the entire gag region according to their potential for immune escape and their effect on disease progression.

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Section: Fig 1 Comparison Of Individual Residue Entropies Between Tmentioning

confidence: 78%

An Integrative Bioinformatic Approach for Studying Escape Mutations in Human Immunodeficiency Virus Type 1gagin the Pumwani Sex Worker Cohort

Peters¹,

Mendoza

Capiña

et al. 2008

J Virol

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“…The available experimental and epidemiologic data point to structural and functional features of B*5802 that set it apart from the other members of the B58 supertype with regard to its capacity to respond to HIV-1 subtype C peptides. Specifically, it has been suggested that changes in amino acid side chains (94I3T, 95I3L, and 97R3W) in the ␣-2 helix of HLA class I molecules affect the key structures of the antigen binding groove such as the tyrosine bed and the F-pocket (2,12,21,26), thereby impairing the presentation of immunodominant HIV-1 peptides.…”

Section: Discussionmentioning

confidence: 99%

Human Leukocyte Antigen B58 Supertype and Human Immunodeficiency Virus Type 1 Infection in Native Africans

Lazaryan¹,

Lobashevsky²,

Mulenga³

et al. 2006

J Virol

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Human leukocyte antigen (HLA) class I alleles can be grouped into supertypes according to their shared peptide binding properties. We examined alleles of the HLA-B58 supertype (B58s) in treatment-naïve human immunodeficiency virus type 1 (HIV-1)-seropositive Africans (423 Zambians and 202 Rwandans). HLA-B and HLA-C alleles were resolved to four digits by a combination of molecular methods, and their respective associations with outcomes of HIV-1 infection were analyzed by statistical procedures appropriate for continuous or categorical data. The effects of the individual alleles on natural HIV-1 infection were heterogeneous. In HIV-1 subtype C-infected Zambians, the mean viral load (VL) was lower among B*5703 (P ‫؍‬ 0.01) or B*5703-Cw*18 (P < 0.001) haplotype carriers and higher among B*5802 (P ‫؍‬ 0.02) or B*5802-Cw*0602 (P ‫؍‬ 0.03) carriers. The B*5801-Cw*03 haplotype showed an association with low VL (P ‫؍‬ 0.05), whereas B*5801 as a whole did not. Rwandans with HIV-1 subtype A infection showed associations of B*5703 and B*5802 with slow (P ‫؍‬ 0.06) and rapid (P ‫؍‬ 0.003) disease progression, respectively. In neither population were B*1516-

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“…Correct tetramer folding was confirmed by staining well-characterized specific cytotoxic T cell lines (18,19). Three of the four NK clones bound to HLA-A*2402 tetramers containing different epitope peptides from HIV-1 nef, HIV-1 gag p17, and human cytomegalovirus (Fig.…”

Section: Kir3dl1 Binds To Hla-a*2402 Tetramersmentioning

confidence: 99%

“…One is that changes in the orientation of D1 and D2 caused by leucine 283 alters the elbow surface to favor interaction with B*5703. The other is that the unusual central bulge of the 11-mer KAF peptide when bound to B*5703 (19) favors binding to the AЈB loop of the D1 domain of 3DL1*005, providing additional interactions that could increase the binding affinity. Further study is needed to determine the contribution of these two potential mechanisms.…”

Section: Structural Models For the Distinctive Hla Class I Specificitmentioning

confidence: 99%

Cutting Edge: Allele-Specific and Peptide-Dependent Interactions between KIR3DL1 and HLA-A and HLA-B

Thananchai

Gillespie

Martin

et al. 2007

The Journal of Immunology

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207

215

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Although it is clear that KIR3DL1 recognizes Bw4+ HLA-B, the role of Bw4+ HLA-A allotypes as KIR3DL1 ligands is controversial. We therefore examined the binding of tetrameric HLA-A and –B complexes, including HLA*2402, a common Bw4+ HLA-A allotype, to KIR3DL1*001, *005, *007, and *1502 allotypes. Only Bw4+ tetramers bound KIR3DL1. Three of four HLA-A*2402 tetramers bound one or more KIR3DL1 allotypes and all four KIR3DL1 allotypes bound to one or more HLA-A*2402 tetramers, but with different binding specificities. Only KIR3DL1*005 bound both HLA-A*2402 and HLA-B*5703 tetramers. HLA-A*2402-expressing target cells were resistant to lysis by NK cells expressing KIR3DL1*001 or *005. This study shows that HLA-A*2402 is a ligand for KIR3DL1 and demonstrates how the binding of KIR3DL1 to Bw4+ ligands depends upon the bound peptide as well as HLA and KIR3DL1 polymorphism.

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Structures of Three HIV-1 HLA-B*5703-Peptide Complexes and Identification of Related HLAs Potentially Associated with Long-Term Nonprogression

Cited by 70 publications

References 56 publications

An Integrative Bioinformatic Approach for Studying Escape Mutations in Human Immunodeficiency Virus Type 1gagin the Pumwani Sex Worker Cohort

An Integrative Bioinformatic Approach for Studying Escape Mutations in Human Immunodeficiency Virus Type 1gagin the Pumwani Sex Worker Cohort

Human Leukocyte Antigen B58 Supertype and Human Immunodeficiency Virus Type 1 Infection in Native Africans

Cutting Edge: Allele-Specific and Peptide-Dependent Interactions between KIR3DL1 and HLA-A and HLA-B

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