An HLA‐B35‐restricted epitope modified at an anchor residue results in an antagonist peptide

Dong, Tao; Boyd, D. R. J.; Rosenberg, William; Alp, N; Takiguchi, Masafumi; McMichael, Andrew J.; Rowland‐Jones, Sarah

doi:10.1002/eji.1830260210

Cited by 42 publications

(21 citation statements)

References 36 publications

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“…The low binding affinity of M1 peptides is likely because of their size and/or lack of the 2 characteristic B*0702 anchor residues. This is consistent with reports of other influenza matrix ligands that lack a characteristic class I anchor residue and exhibit a low binding affinity (15). With the exception of the matrix peptides, the ligands reported here are consistent in size, binding affinity, and sequence with previously reported B*0702 epitopes of viral and human origin (9).…”

Section: Comparative Mass Spectrometry Reveals 7 Influenza Hla B*0702supporting

confidence: 91%

HLA class I molecules consistently present internal influenza epitopes

Wahl¹,

Schafer²,

Bardet³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Section: Comparative Mass Spectrometry Reveals 7 Influenza Hla B*0702supporting

confidence: 91%

HLA class I molecules consistently present internal influenza epitopes

Wahl¹,

Schafer²,

Bardet³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…Of special interest, HLA-B‫-1053ء‬positive cells infected with influenza virus A/NL/95-NP M426I were poorly recognized by NP 418-426 -specific T-cell clones. Since the NP M426I mutant epitope retained its capacity to bind to HLA-B‫,1053ء‬ it may have undergone conformational changes in T-cell receptor contact residues, preventing recognition by CTL, as has been described previously for another HLA-B‫-1053ء‬restricted epitope (15). Conservative amino acid substitutions at the anchor residues of the epitopes PB1 591-599 (VSDGGPNLY), NP [44][45][46][47][48][49][50][51][52] (CTELKLSDY), and NP 174-184 (RRSGAAGAAVK) also affected viral fitness.…”

Section: Discussionmentioning

confidence: 77%

Functional Constraints of Influenza A Virus Epitopes Limit Escape from Cytotoxic T Lymphocytes

Berkhoff

Wit

Geelhoed-Mieras

et al. 2005

J Virol

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Viruses can exploit a variety of strategies to evade immune surveillance by cytotoxic T lymphocytes (CTL), including the acquisition of mutations in CTL epitopes. Also for influenza A viruses a number of amino acid substitutions in the nucleoprotein (NP) have been associated with escape from CTL. However, other previously identified influenza A virus CTL epitopes are highly conserved, including the immunodominant HLA-A‫-1020ء‬ restricted epitope from the matrix protein, M1 58-66 . We hypothesized that functional constraints were responsible for the conserved nature of influenza A virus CTL epitopes, limiting escape from CTL. To assess the impact of amino acid substitutions in conserved epitopes on viral fitness and recognition by specific CTL, we performed a mutational analysis of CTL epitopes. Both alanine replacements and more conservative substitutions were introduced at various positions of different influenza A virus CTL epitopes. Alanine replacements for each of the nine amino acids of the M1 58-66 epitope were tolerated to various extents, except for the anchor residue at the second position. Substitution of anchor residues in other influenza A virus CTL epitopes also affected viral fitness. Viable mutant viruses were used in CTL recognition experiments. The results are discussed in the light of the possibility of influenza viruses to escape from specific CTL. It was speculated that functional constraints limit variation in certain epitopes, especially at anchor residues, explaining the conserved nature of these epitopes. Cytotoxic T lymphocytes (CTL) play an important role in the control of viral infections (10).To evade these CTL responses, viruses can exploit a variety of mechanisms to prevent recognition by specific CTL, including the accumulation of amino acid substitutions in or adjacent to CTL epitopes (28, 39). This strategy has been shown predominantly by certain RNA viruses, such as human immunodeficiency virus (HIV) (7,21,22,35,44,47,48), hepatitis C virus (9, 60), and lymphocytic choriomeningitis virus (36, 46), which are known for their high mutation rate. Also for influenza A viruses, a number of amino acid substitutions in the nucleoprotein (NP) have been associated with escape from human CTL. One of them, the R-to-G substitution at position 384 (R384G), which is at the anchor residues of the HLA-B‫-1080ء‬restricted NP 380-388 and HLA-B‫-5072ء‬restricted NP 383-391 epitopes, resulted in the loss of these epitopes (51,58). This substitution reduced the in vitro virus-specific CTL response in HLA-B‫-5072ء‬positive individuals significantly (2). Although the R384G substitution was tolerated only in the presence of one or more functionally compensating comutations (50, 52), it was fixed rapidly. This was explained by small selective advantages and population dynamics in a theoretical model (19). A third variable epitope in the influenza A virus NP is the HLA-B‫-1053ء‬restricted epitope NP [418][419][420][421][422][423][424][425][426] , which displayed considerable variability in T-cell contact ...

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“…The cultures were restimulated after 14 d using autologous BCLs pulsed with the appropriate peptides. Antigen-specific CD4 + and CD8 + T cell clones were established by limiting dilution of the T cell lines as described previously (66).…”

Section: Methodsmentioning

confidence: 99%

Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals

Ly-H.¹,

Dla.²,

Simmons³

et al. 2008

J. Clin. Invest.

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280

318

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The threat of avian influenza A (H5N1) infection in humans remains a global health concern. Current influenza vaccines stimulate antibody responses against the surface glycoproteins but are ineffective against strains that have undergone significant antigenic variation. An alternative approach is to stimulate pre-existing memory T cells established by seasonal human influenza A infection that could cross-react with H5N1 by targeting highly conserved internal proteins. To determine how common cross-reactive T cells are, we performed a comprehensive ex vivo analysis of cross-reactive CD4 + and CD8 +

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An HLA‐B35‐restricted epitope modified at an anchor residue results in an antagonist peptide

Cited by 42 publications

References 36 publications

HLA class I molecules consistently present internal influenza epitopes

HLA class I molecules consistently present internal influenza epitopes

Functional Constraints of Influenza A Virus Epitopes Limit Escape from Cytotoxic T Lymphocytes

Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals

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