Broadly targeted CD8 + T cell responses restricted by major histocompatibility complex E
Major histocompatibility complex (MHC)-E is a highly conserved, ubiquitously expressed, nonclassical, MHC-Ib molecule with limited polymorphism primarily involved in regulation of NK cell reactivity via interaction with NKG2/CD94 receptors. We found that vaccination of rhesus macaques with Rh157.5/.4 gene-deleted rhesus Cytomegalovirus (RhCMV) vectors uniquely diverts MHC-E function to presentation of highly diverse peptide epitopes to CD8α/β + T cells, approximately 4 distinct epitopes per 100 amino acids, in all tested protein antigens. Computational structural analysis revealed that a relatively stable, open binding groove in MHC-E attains broad peptide binding specificity by imposing a similar backbone configuration on bound peptides with few restrictions based on amino acid side chains. Since MHC-E is up-regulated on cells infected with HIV/SIV and other persistent viruses to evade NK cell activity, 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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- Oregon Health & Science Univ., Beaverton, OR (United States). Vaccine and Gene Therapy Inst. and Oregon National Primate Research Center
- Univ. of Oxford (United Kingdom). Nuffield Dept. of Medicine
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Biology and Biophysics Group
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Biology and Biophysics Group; New Mexico Consortium, Los Alamos, NM (United States)
- Publication Date:
- Report Number(s):
- LA-UR-15-24868
Journal ID: ISSN 0036-8075; 1095-9203 (Electronic)
- Grant/Contract Number:
- AC52-06NA25396; 1K01DK094941; 5U01DK89572; DK104211; 5-CDA2014210-A-N; 1R01DK081166
- Type:
- Published Article
- Journal Name:
- Science
- Additional Journal Information:
- Journal Volume: 351; Journal Issue: 6274; Journal ID: ISSN 0036-8075
- Publisher:
- AAAS
- Research Org:
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
- Sponsoring Org:
- USDOE National Nuclear Security Administration (NNSA); National Institutes of Health (NIH); Work for Others (WFO)
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Biological Science; CD8+ T; Major histocompatibility complex E; MHC-E; HIV
- OSTI Identifier:
- 1355834
- Alternate Identifier(s):
- OSTI ID: 1304811
Hansen, Scott G., Wu, Helen L., Burwits, Benjamin J., Hughes, Colette M., Hammond, Katherine B., Ventura, Abigail B., Reed, Jason S., Gilbride, Roxanne M., Ainslie, Emily, Morrow, David W., Ford, Julia C., Selseth, Andrea N., Pathak, Reesab, Malouli, Daniel, Legasse, Alfred W., Axthelm, Michael K., Nelson, Jay A., Gillespie, Geraldine M., Walters, Lucy C., Brackenridge, Simon, Sharpe, Hannah R., Lopez, Cesar Augusto, Fruh, Klaus, Korber, Bette Tina, McMichael, Andrew J., Gnanakaran, Sandrasegaram, Sacha, Jonah B., and Picker, Louis J.. Broadly targeted CD8+ T cell responses restricted by major histocompatibility complex E. United States: N. p.,
Web. doi:10.1126/science.aac9475.
Hansen, Scott G., Wu, Helen L., Burwits, Benjamin J., Hughes, Colette M., Hammond, Katherine B., Ventura, Abigail B., Reed, Jason S., Gilbride, Roxanne M., Ainslie, Emily, Morrow, David W., Ford, Julia C., Selseth, Andrea N., Pathak, Reesab, Malouli, Daniel, Legasse, Alfred W., Axthelm, Michael K., Nelson, Jay A., Gillespie, Geraldine M., Walters, Lucy C., Brackenridge, Simon, Sharpe, Hannah R., Lopez, Cesar Augusto, Fruh, Klaus, Korber, Bette Tina, McMichael, Andrew J., Gnanakaran, Sandrasegaram, Sacha, Jonah B., & Picker, Louis J.. Broadly targeted CD8+ T cell responses restricted by major histocompatibility complex E. United States. doi:10.1126/science.aac9475.
Hansen, Scott G., Wu, Helen L., Burwits, Benjamin J., Hughes, Colette M., Hammond, Katherine B., Ventura, Abigail B., Reed, Jason S., Gilbride, Roxanne M., Ainslie, Emily, Morrow, David W., Ford, Julia C., Selseth, Andrea N., Pathak, Reesab, Malouli, Daniel, Legasse, Alfred W., Axthelm, Michael K., Nelson, Jay A., Gillespie, Geraldine M., Walters, Lucy C., Brackenridge, Simon, Sharpe, Hannah R., Lopez, Cesar Augusto, Fruh, Klaus, Korber, Bette Tina, McMichael, Andrew J., Gnanakaran, Sandrasegaram, Sacha, Jonah B., and Picker, Louis J.. 2016.
"Broadly targeted CD8+ T cell responses restricted by major histocompatibility complex E". United States.
doi:10.1126/science.aac9475.
@article{osti_1355834,
title = {Broadly targeted CD8+ T cell responses restricted by major histocompatibility complex E},
author = {Hansen, Scott G. and Wu, Helen L. and Burwits, Benjamin J. and Hughes, Colette M. and Hammond, Katherine B. and Ventura, Abigail B. and Reed, Jason S. and Gilbride, Roxanne M. and Ainslie, Emily and Morrow, David W. and Ford, Julia C. and Selseth, Andrea N. and Pathak, Reesab and Malouli, Daniel and Legasse, Alfred W. and Axthelm, Michael K. and Nelson, Jay A. and Gillespie, Geraldine M. and Walters, Lucy C. and Brackenridge, Simon and Sharpe, Hannah R. and Lopez, Cesar Augusto and Fruh, Klaus and Korber, Bette Tina and McMichael, Andrew J. and Gnanakaran, Sandrasegaram and Sacha, Jonah B. and Picker, Louis J.},
abstractNote = {Major histocompatibility complex (MHC)-E is a highly conserved, ubiquitously expressed, nonclassical, MHC-Ib molecule with limited polymorphism primarily involved in regulation of NK cell reactivity via interaction with NKG2/CD94 receptors. We found that vaccination of rhesus macaques with Rh157.5/.4 gene-deleted rhesus Cytomegalovirus (RhCMV) vectors uniquely diverts MHC-E function to presentation of highly diverse peptide epitopes to CD8α/β+ T cells, approximately 4 distinct epitopes per 100 amino acids, in all tested protein antigens. Computational structural analysis revealed that a relatively stable, open binding groove in MHC-E attains broad peptide binding specificity by imposing a similar backbone configuration on bound peptides with few restrictions based on amino acid side chains. Since MHC-E is up-regulated on cells infected with HIV/SIV and other persistent viruses to evade NK cell activity, 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.},
doi = {10.1126/science.aac9475},
journal = {Science},
number = 6274,
volume = 351,
place = {United States},
year = {2016},
month = {2}
}