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Epitope mapping of HIV-specific CD8+ T cells in a cohort dominated by clade A1 infection.

McKinnon LR, Mao X, Kimani J, Wachihi C, Semeniuk C, Mendoza M, Liang B, Luo M, Fowke KR, Plummer FA, Ball TB - PLoS ONE (2009)

Bottom Line: Population differences in CD8+ T cell epitope specificity will need to be understood if vaccines are to be effective in multiple geographic regions.While the majority of BDEs (69%) were recognized in this population, nearly half of responsive OLPs (47%) did not contain described epitopes.Expansion of these studies will be critical to understand population differences in CD8 epitope recognition.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada. sijuisijali@gmail.com

ABSTRACT

Background: CD8+ T cell responses are often detected at large magnitudes in HIV-infected subjects, and eliciting these responses is the central aim of many HIV-1 vaccine strategies. Population differences in CD8+ T cell epitope specificity will need to be understood if vaccines are to be effective in multiple geographic regions.

Methodology/principal findings: In a large Kenyan cohort, we compared responsive CD8+ T cell HIV-1 Env overlapping peptides (OLPs) to Best Defined Epitopes (BDEs), many of which have been defined in clade B infection. While the majority of BDEs (69%) were recognized in this population, nearly half of responsive OLPs (47%) did not contain described epitopes. Recognition frequencies of BDEs were inversely correlated to epitopic sequence differences between clade A1 and BDE (P = 0.019), and positively selected residues were more frequent in "new" OLPs (without BDEs). We assessed the impact of HLA and TAP binding on epitope recognition frequencies, focusing on predicted and actual epitopes in the HLA B7 supertype.

Conclusions/significance: Although many previously described CD8 epitopes were recognized, several novel CD8 epitopes were defined in this population, implying that epitope mapping efforts have not been completely exhausted. Expansion of these studies will be critical to understand population differences in CD8 epitope recognition.

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Related in: MedlinePlus

OLP-147 and 149 represent clade A1-specific epitopes.These OLPs associate with HLA-B*57 expression (Table 2) and with the anchor residues that have been defined for the HLA-B*57 binding motif a). Alignments of the optimal epitope within OLP-149 demonstrate that in other clades, this epitope would not likely be presented by HLA-B*57 b).
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pone-0006965-g002: OLP-147 and 149 represent clade A1-specific epitopes.These OLPs associate with HLA-B*57 expression (Table 2) and with the anchor residues that have been defined for the HLA-B*57 binding motif a). Alignments of the optimal epitope within OLP-149 demonstrate that in other clades, this epitope would not likely be presented by HLA-B*57 b).

Mentions: We observed some examples of frequently recognized epitopes that appear to be clade A1-specific. OLPs-147, 148, and 149 were frequently recognized and contain no described epitopes to date. These OLPs were weakly associated with HLA-B*57 expression, but these associations did not survive multiple test comparisons (described below, Table S2). Two potential epitopes within these OLPs, VSGFLALAW and RSIRLVSGF, fit the HLA-B*57 binding motif (Fig. 2a), and we confirmed these as recognizable epitopes in Elispot assays using PBMCs from HLA-B*57+ subjects (not shown). These responses were often immunodominant; OLP-149, where targeted, was typically the strongest Env-specific response, and pool 23 (containing OLP147, 148, and 149) was the dominant Env pool in >75% of B*57+ subjects tested (not shown). The clade B version of this epitope contains aspartic acid at position 2 in the epitope (Fig. 2b). Because the HLA-B*57 binding motif prefers alanine, threonine, or serine as position 2 anchors, this epitope does not appear to be available in clade B, providing a possible explanation as to why it has yet to be described. Given the additional differences in clades C and D in this region, it is likely that these immunodominant epitopes are clade A1-specific.


Epitope mapping of HIV-specific CD8+ T cells in a cohort dominated by clade A1 infection.

McKinnon LR, Mao X, Kimani J, Wachihi C, Semeniuk C, Mendoza M, Liang B, Luo M, Fowke KR, Plummer FA, Ball TB - PLoS ONE (2009)

OLP-147 and 149 represent clade A1-specific epitopes.These OLPs associate with HLA-B*57 expression (Table 2) and with the anchor residues that have been defined for the HLA-B*57 binding motif a). Alignments of the optimal epitope within OLP-149 demonstrate that in other clades, this epitope would not likely be presented by HLA-B*57 b).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2735720&req=5

pone-0006965-g002: OLP-147 and 149 represent clade A1-specific epitopes.These OLPs associate with HLA-B*57 expression (Table 2) and with the anchor residues that have been defined for the HLA-B*57 binding motif a). Alignments of the optimal epitope within OLP-149 demonstrate that in other clades, this epitope would not likely be presented by HLA-B*57 b).
Mentions: We observed some examples of frequently recognized epitopes that appear to be clade A1-specific. OLPs-147, 148, and 149 were frequently recognized and contain no described epitopes to date. These OLPs were weakly associated with HLA-B*57 expression, but these associations did not survive multiple test comparisons (described below, Table S2). Two potential epitopes within these OLPs, VSGFLALAW and RSIRLVSGF, fit the HLA-B*57 binding motif (Fig. 2a), and we confirmed these as recognizable epitopes in Elispot assays using PBMCs from HLA-B*57+ subjects (not shown). These responses were often immunodominant; OLP-149, where targeted, was typically the strongest Env-specific response, and pool 23 (containing OLP147, 148, and 149) was the dominant Env pool in >75% of B*57+ subjects tested (not shown). The clade B version of this epitope contains aspartic acid at position 2 in the epitope (Fig. 2b). Because the HLA-B*57 binding motif prefers alanine, threonine, or serine as position 2 anchors, this epitope does not appear to be available in clade B, providing a possible explanation as to why it has yet to be described. Given the additional differences in clades C and D in this region, it is likely that these immunodominant epitopes are clade A1-specific.

Bottom Line: Population differences in CD8+ T cell epitope specificity will need to be understood if vaccines are to be effective in multiple geographic regions.While the majority of BDEs (69%) were recognized in this population, nearly half of responsive OLPs (47%) did not contain described epitopes.Expansion of these studies will be critical to understand population differences in CD8 epitope recognition.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada. sijuisijali@gmail.com

ABSTRACT

Background: CD8+ T cell responses are often detected at large magnitudes in HIV-infected subjects, and eliciting these responses is the central aim of many HIV-1 vaccine strategies. Population differences in CD8+ T cell epitope specificity will need to be understood if vaccines are to be effective in multiple geographic regions.

Methodology/principal findings: In a large Kenyan cohort, we compared responsive CD8+ T cell HIV-1 Env overlapping peptides (OLPs) to Best Defined Epitopes (BDEs), many of which have been defined in clade B infection. While the majority of BDEs (69%) were recognized in this population, nearly half of responsive OLPs (47%) did not contain described epitopes. Recognition frequencies of BDEs were inversely correlated to epitopic sequence differences between clade A1 and BDE (P = 0.019), and positively selected residues were more frequent in "new" OLPs (without BDEs). We assessed the impact of HLA and TAP binding on epitope recognition frequencies, focusing on predicted and actual epitopes in the HLA B7 supertype.

Conclusions/significance: Although many previously described CD8 epitopes were recognized, several novel CD8 epitopes were defined in this population, implying that epitope mapping efforts have not been completely exhausted. Expansion of these studies will be critical to understand population differences in CD8 epitope recognition.

Show MeSH
Related in: MedlinePlus