Broadly targeted CD8+ T cell responses restricted by major histocompatibility complex E

Scott G. Hansen; Helen L. Wu; Benjamin J. Burwitz; Colette M. Hughes; Katherine B. Hammond; Abigail B. Ventura; Jason S. Reed; Roxanne M. Gilbride; Emily Ainslie; David W. Morrow; Julia C. Ford; Andrea N. Selseth; Reesab Pathak; Daniel Malouli; Alfred W. Legasse; Michael K. Axthelm; Jay A. Nelson; Geraldine M. Gillespie; Lucy C. Walters; Simon Brackenridge; Hannah R. Sharpe; César A. López; Klaus Früh; Bette T. Korber; Andrew J. McMichael; S. Gnanakaran; Jonah B. Sacha; Louis J. Picker

doi:10.1126/science.aac9475

Broadly targeted CD8⁺ T cell responses restricted by major histocompatibility complex E

Scott G. Hansen, Helen L. Wu, Benjamin J. Burwitz, Colette M. Hughes, Katherine B. Hammond, Abigail B. Ventura, Jason S. Reed, Roxanne M. Gilbride, Emily Ainslie, David W. Morrow, Julia C. Ford, Andrea N. Selseth, Reesab Pathak, Daniel Malouli, Alfred W. Legasse, Michael K. Axthelm, Jay A. Nelson, Geraldine M. Gillespie, Lucy C. Walters, Simon BrackenridgeHannah R. Sharpe, César A. López, Klaus Früh, Bette T. Korber, Andrew J. McMichael, S. Gnanakaran, Jonah B. Sacha, Louis J. Picker

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Abstract

Major histocompatibility complex E (MHC-E) is a highly conserved, ubiquitously expressed, nonclassical MHC class Ib molecule with limited polymorphism that is primarily involved in the regulation of natural killer (NK) cells. We found that vaccinating rhesus macaques with rhesus cytomegalovirus vectors in which genes Rh157.5 and Rh157.4 are deleted results in MHC-E-restricted presentation of highly varied peptide epitopes to CD8αβ⁺ T cells, at ∼4 distinct epitopes per 100 amino acids in all tested antigens. Computational structural analysis revealed that MHC-E provides heterogeneous chemical environments for diverse side-chain interactions within a stable, open binding groove. Because MHC-E is up-regulated to evade NK cell activity in cells infected with HIV, simian immunodeficiency virus, and other persistent viruses, MHC-E-restricted CD8⁺ T cell responses have the potential to exploit pathogen immune-evasion adaptations, a capability that might endow these unconventional responses with superior efficacy.

Original language	English (US)
Pages (from-to)	714-720
Number of pages	7
Journal	Science
Volume	351
Issue number	6274
DOIs	https://doi.org/10.1126/science.aac9475
State	Published - Feb 12 2016

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Hansen, S. G., Wu, H. L., Burwitz, B. J., Hughes, C. M., Hammond, K. B., Ventura, A. B., Reed, J. S., Gilbride, R. M., Ainslie, E., Morrow, D. W., Ford, J. C., Selseth, A. N., Pathak, R., Malouli, D., Legasse, A. W., Axthelm, M. K., Nelson, J. A., Gillespie, G. M., Walters, L. C., ... Picker, L. J. (2016). Broadly targeted CD8⁺ T cell responses restricted by major histocompatibility complex E. Science, 351(6274), 714-720. https://doi.org/10.1126/science.aac9475

Hansen, SG, Wu, HL, Burwitz, BJ, Hughes, CM, Hammond, KB, Ventura, AB, Reed, JS, Gilbride, RM, Ainslie, E, Morrow, DW, Ford, JC, Selseth, AN, Pathak, R, Malouli, D, Legasse, AW, Axthelm, MK, Nelson, JA, Gillespie, GM, Walters, LC, Brackenridge, S, Sharpe, HR, López, CA, Früh, K, Korber, BT, McMichael, AJ, Gnanakaran, S, Sacha, JB & Picker, LJ 2016, 'Broadly targeted CD8⁺ T cell responses restricted by major histocompatibility complex E', Science, vol. 351, no. 6274, pp. 714-720. https://doi.org/10.1126/science.aac9475

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title = "Broadly targeted CD8+ T cell responses restricted by major histocompatibility complex E",

abstract = "Major histocompatibility complex E (MHC-E) is a highly conserved, ubiquitously expressed, nonclassical MHC class Ib molecule with limited polymorphism that is primarily involved in the regulation of natural killer (NK) cells. We found that vaccinating rhesus macaques with rhesus cytomegalovirus vectors in which genes Rh157.5 and Rh157.4 are deleted results in MHC-E-restricted presentation of highly varied peptide epitopes to CD8αβ+ T cells, at ∼4 distinct epitopes per 100 amino acids in all tested antigens. Computational structural analysis revealed that MHC-E provides heterogeneous chemical environments for diverse side-chain interactions within a stable, open binding groove. Because MHC-E is up-regulated to evade NK cell activity in cells infected with HIV, simian immunodeficiency virus, and other persistent viruses, MHC-E-restricted CD8+ T cell responses have the potential to exploit pathogen immune-evasion adaptations, a capability that might endow these unconventional responses with superior efficacy.",

author = "Hansen, {Scott G.} and Wu, {Helen L.} and Burwitz, {Benjamin J.} and Hughes, {Colette M.} and Hammond, {Katherine B.} and Ventura, {Abigail B.} and Reed, {Jason S.} and Gilbride, {Roxanne M.} and Emily Ainslie and Morrow, {David W.} and Ford, {Julia C.} and Selseth, {Andrea N.} and Reesab Pathak and Daniel Malouli and Legasse, {Alfred W.} and Axthelm, {Michael K.} and Nelson, {Jay A.} and Gillespie, {Geraldine M.} and Walters, {Lucy C.} and Simon Brackenridge and Sharpe, {Hannah R.} and L{\'o}pez, {C{\'e}sar A.} and Klaus Fr{\"u}h and Korber, {Bette T.} and McMichael, {Andrew J.} and S. Gnanakaran and Sacha, {Jonah B.} and Picker, {Louis J.}",

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doi = "10.1126/science.aac9475",

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AU - Hansen, Scott G.

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AU - Hammond, Katherine B.

AU - Ventura, Abigail B.

AU - Reed, Jason S.

AU - Gilbride, Roxanne M.

AU - Ainslie, Emily

AU - Morrow, David W.

AU - Ford, Julia C.

AU - Selseth, Andrea N.

AU - Pathak, Reesab

AU - Malouli, Daniel

AU - Legasse, Alfred W.

AU - Axthelm, Michael K.

AU - Nelson, Jay A.

AU - Gillespie, Geraldine M.

AU - Walters, Lucy C.

AU - Brackenridge, Simon

AU - Sharpe, Hannah R.

AU - López, César A.

AU - Früh, Klaus

AU - Korber, Bette T.

AU - McMichael, Andrew J.

AU - Gnanakaran, S.

AU - Sacha, Jonah B.

AU - Picker, Louis J.

PY - 2016/2/12

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N2 - Major histocompatibility complex E (MHC-E) is a highly conserved, ubiquitously expressed, nonclassical MHC class Ib molecule with limited polymorphism that is primarily involved in the regulation of natural killer (NK) cells. We found that vaccinating rhesus macaques with rhesus cytomegalovirus vectors in which genes Rh157.5 and Rh157.4 are deleted results in MHC-E-restricted presentation of highly varied peptide epitopes to CD8αβ+ T cells, at ∼4 distinct epitopes per 100 amino acids in all tested antigens. Computational structural analysis revealed that MHC-E provides heterogeneous chemical environments for diverse side-chain interactions within a stable, open binding groove. Because MHC-E is up-regulated to evade NK cell activity in cells infected with HIV, simian immunodeficiency virus, and other persistent viruses, MHC-E-restricted CD8+ T cell responses have the potential to exploit pathogen immune-evasion adaptations, a capability that might endow these unconventional responses with superior efficacy.

AB - Major histocompatibility complex E (MHC-E) is a highly conserved, ubiquitously expressed, nonclassical MHC class Ib molecule with limited polymorphism that is primarily involved in the regulation of natural killer (NK) cells. We found that vaccinating rhesus macaques with rhesus cytomegalovirus vectors in which genes Rh157.5 and Rh157.4 are deleted results in MHC-E-restricted presentation of highly varied peptide epitopes to CD8αβ+ T cells, at ∼4 distinct epitopes per 100 amino acids in all tested antigens. Computational structural analysis revealed that MHC-E provides heterogeneous chemical environments for diverse side-chain interactions within a stable, open binding groove. Because MHC-E is up-regulated to evade NK cell activity in cells infected with HIV, simian immunodeficiency virus, and other persistent viruses, MHC-E-restricted CD8+ T cell responses have the potential to exploit pathogen immune-evasion adaptations, a capability that might endow these unconventional responses with superior efficacy.

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Broadly targeted CD8⁺ T cell responses restricted by major histocompatibility complex E

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