Epitope length variants balance protective immune responses and viral escape in HIV-1 infection

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Epitope length variants balance protective immune responses and viral escape in HIV-1 infection. / Pymm, Phillip; Tenzer, Stefan; Wee, Edmund; Weimershaus, Mirjana; Burgevin, Anne; Kollnberger, Simon; Gerstoft, Jan; Josephs, Tracy M.; Ladell, Kristin; McLaren, James E.; Appay, Victor; Price, David A.; Fugger, Lars; Bell, John I.; Schild, Hansjörg; van Endert, Peter; Harkiolaki, Maria; Iversen, Astrid K.N.

In: Cell Reports, Vol. 38, No. 9, 110449, 2022.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Pymm, P, Tenzer, S, Wee, E, Weimershaus, M, Burgevin, A, Kollnberger, S, Gerstoft, J, Josephs, TM, Ladell, K, McLaren, JE, Appay, V, Price, DA, Fugger, L, Bell, JI, Schild, H, van Endert, P, Harkiolaki, M & Iversen, AKN 2022, 'Epitope length variants balance protective immune responses and viral escape in HIV-1 infection', Cell Reports, vol. 38, no. 9, 110449. https://doi.org/10.1016/j.celrep.2022.110449

APA

Pymm, P., Tenzer, S., Wee, E., Weimershaus, M., Burgevin, A., Kollnberger, S., Gerstoft, J., Josephs, T. M., Ladell, K., McLaren, J. E., Appay, V., Price, D. A., Fugger, L., Bell, J. I., Schild, H., van Endert, P., Harkiolaki, M., & Iversen, A. K. N. (2022). Epitope length variants balance protective immune responses and viral escape in HIV-1 infection. Cell Reports, 38(9), [110449]. https://doi.org/10.1016/j.celrep.2022.110449

Vancouver

Pymm P, Tenzer S, Wee E, Weimershaus M, Burgevin A, Kollnberger S et al. Epitope length variants balance protective immune responses and viral escape in HIV-1 infection. Cell Reports. 2022;38(9). 110449. https://doi.org/10.1016/j.celrep.2022.110449

Author

Pymm, Phillip ; Tenzer, Stefan ; Wee, Edmund ; Weimershaus, Mirjana ; Burgevin, Anne ; Kollnberger, Simon ; Gerstoft, Jan ; Josephs, Tracy M. ; Ladell, Kristin ; McLaren, James E. ; Appay, Victor ; Price, David A. ; Fugger, Lars ; Bell, John I. ; Schild, Hansjörg ; van Endert, Peter ; Harkiolaki, Maria ; Iversen, Astrid K.N. / Epitope length variants balance protective immune responses and viral escape in HIV-1 infection. In: Cell Reports. 2022 ; Vol. 38, No. 9.

Bibtex

@article{15344b00a795498da70d8a58b67faea5,

title = "Epitope length variants balance protective immune responses and viral escape in HIV-1 infection",

abstract = "Cytotoxic T lymphocyte (CTL) and natural killer (NK) cell responses to a single optimal 10-mer epitope (KK10) in the human immunodeficiency virus type-1 (HIV-1) protein p24Gag are associated with enhanced immune control in patients expressing human leukocyte antigen (HLA)-B∗27:05. We find that proteasomal activity generates multiple length variants of KK10 (4–14 amino acids), which bind TAP and HLA-B∗27:05. However, only epitope forms ≥8 amino acids evoke peptide length-specific and cross-reactive CTL responses. Structural analyses reveal that all epitope forms bind HLA-B∗27:05 via a conserved N-terminal motif, and competition experiments show that the truncated epitope forms outcompete immunogenic epitope forms for binding to HLA-B∗27:05. Common viral escape mutations abolish (L136M) or impair (R132K) production of KK10 and longer epitope forms. Peptide length influences how well the inhibitory NK cell receptor KIR3DL1 binds HLA-B∗27:05 peptide complexes and how intraepitope mutations affect this interaction. These results identify a viral escape mechanism from CTL and NK responses based on differential antigen processing and peptide competition.",

keywords = "crystal structures, cytotoxic T lymphocytes, differential antigen processing, HIV-1, HLA-B27:05, immune-response inhibition, KIR3DL1, natural killer cells, peptide competition, viral escape",

author = "Phillip Pymm and Stefan Tenzer and Edmund Wee and Mirjana Weimershaus and Anne Burgevin and Simon Kollnberger and Jan Gerstoft and Josephs, {Tracy M.} and Kristin Ladell and McLaren, {James E.} and Victor Appay and Price, {David A.} and Lars Fugger and Bell, {John I.} and Hansj{\"o}rg Schild and {van Endert}, Peter and Maria Harkiolaki and Iversen, {Astrid K.N.}",

note = "Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2022",

doi = "10.1016/j.celrep.2022.110449",

language = "English",

volume = "38",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "9",

}

RIS

TY - JOUR

T1 - Epitope length variants balance protective immune responses and viral escape in HIV-1 infection

AU - Pymm, Phillip

AU - Tenzer, Stefan

AU - Wee, Edmund

AU - Weimershaus, Mirjana

AU - Burgevin, Anne

AU - Kollnberger, Simon

AU - Gerstoft, Jan

AU - Josephs, Tracy M.

AU - Ladell, Kristin

AU - McLaren, James E.

AU - Appay, Victor

AU - Price, David A.

AU - Fugger, Lars

AU - Bell, John I.

AU - Schild, Hansjörg

AU - van Endert, Peter

AU - Harkiolaki, Maria

AU - Iversen, Astrid K.N.

PY - 2022

Y1 - 2022

N2 - Cytotoxic T lymphocyte (CTL) and natural killer (NK) cell responses to a single optimal 10-mer epitope (KK10) in the human immunodeficiency virus type-1 (HIV-1) protein p24Gag are associated with enhanced immune control in patients expressing human leukocyte antigen (HLA)-B∗27:05. We find that proteasomal activity generates multiple length variants of KK10 (4–14 amino acids), which bind TAP and HLA-B∗27:05. However, only epitope forms ≥8 amino acids evoke peptide length-specific and cross-reactive CTL responses. Structural analyses reveal that all epitope forms bind HLA-B∗27:05 via a conserved N-terminal motif, and competition experiments show that the truncated epitope forms outcompete immunogenic epitope forms for binding to HLA-B∗27:05. Common viral escape mutations abolish (L136M) or impair (R132K) production of KK10 and longer epitope forms. Peptide length influences how well the inhibitory NK cell receptor KIR3DL1 binds HLA-B∗27:05 peptide complexes and how intraepitope mutations affect this interaction. These results identify a viral escape mechanism from CTL and NK responses based on differential antigen processing and peptide competition.

AB - Cytotoxic T lymphocyte (CTL) and natural killer (NK) cell responses to a single optimal 10-mer epitope (KK10) in the human immunodeficiency virus type-1 (HIV-1) protein p24Gag are associated with enhanced immune control in patients expressing human leukocyte antigen (HLA)-B∗27:05. We find that proteasomal activity generates multiple length variants of KK10 (4–14 amino acids), which bind TAP and HLA-B∗27:05. However, only epitope forms ≥8 amino acids evoke peptide length-specific and cross-reactive CTL responses. Structural analyses reveal that all epitope forms bind HLA-B∗27:05 via a conserved N-terminal motif, and competition experiments show that the truncated epitope forms outcompete immunogenic epitope forms for binding to HLA-B∗27:05. Common viral escape mutations abolish (L136M) or impair (R132K) production of KK10 and longer epitope forms. Peptide length influences how well the inhibitory NK cell receptor KIR3DL1 binds HLA-B∗27:05 peptide complexes and how intraepitope mutations affect this interaction. These results identify a viral escape mechanism from CTL and NK responses based on differential antigen processing and peptide competition.

KW - crystal structures

KW - cytotoxic T lymphocytes

KW - differential antigen processing

KW - HIV-1

KW - HLA-B27:05

KW - immune-response inhibition

KW - KIR3DL1

KW - natural killer cells

KW - peptide competition

KW - viral escape

U2 - 10.1016/j.celrep.2022.110449

DO - 10.1016/j.celrep.2022.110449

M3 - Journal article

C2 - 35235807

AN - SCOPUS:85125270755

VL - 38

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 9

M1 - 110449

ER -

ID: 314279016