Abstract
CD8+ T cell recognition of virus-infected cells is characteristically restricted by major histocompatibility complex (MHC) class I, although rare examples of MHC class II restriction have been reported in Cd4-deficient mice and a macaque SIV vaccine trial using a recombinant cytomegalovirus vector. Here, we demonstrate the presence of human leukocyte antigen (HLA) class II-restricted CD8+ T cell responses with antiviral properties in a small subset of HIV-infected individuals. In these individuals, T cell receptor β (TCRβ) analysis revealed that class II-restricted CD8+ T cells underwent clonal expansion and mediated killing of HIV-infected cells. In one case, these cells comprised 12% of circulating CD8+ T cells, and TCRα analysis revealed two distinct co-expressed TCRα chains, with only one contributing to binding of the class II HLA-peptide complex. These data indicate that class II-restricted CD8+ T cell responses can exist in a chronic human viral infection, and may contribute to immune control.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 917-930 |
| Number of pages | 14 |
| Journal | Immunity |
| Volume | 45 |
| Issue number | 4 |
| DOIs | |
| State | Published - Oct 18 2016 |
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Keywords
- CD8 T cells
- HIV
- HLA
- MHC class II
- TCR
- vaccines
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Infectious Diseases
Cite this
Antiviral CD8+ T Cells Restricted by Human Leukocyte Antigen Class II Exist during Natural HIV Infection and Exhibit Clonal Expansion. / Ranasinghe, Srinika; Lamothe, Pedro A.; Soghoian, Damien Z.; Kazer, Samuel W.; Cole, Michael B.; Shalek, Alex K.; Yosef, Nir; Jones, R. Brad; Donaghey, Faith; Nwonu, Chioma; Jani, Priya; Clayton, Gina M.; Crawford, Frances; White, Janice; Montoya, Alana; Power, Karen; Allen, Todd M.; Streeck, Hendrik; Kaufmann, Daniel E.; Picker, Louis; Kappler, John W.; Walker, Bruce D.
In: Immunity, Vol. 45, No. 4, 18.10.2016, p. 917-930.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Antiviral CD8+ T Cells Restricted by Human Leukocyte Antigen Class II Exist during Natural HIV Infection and Exhibit Clonal Expansion
AU - Ranasinghe, Srinika
AU - Lamothe, Pedro A.
AU - Soghoian, Damien Z.
AU - Kazer, Samuel W.
AU - Cole, Michael B.
AU - Shalek, Alex K.
AU - Yosef, Nir
AU - Jones, R. Brad
AU - Donaghey, Faith
AU - Nwonu, Chioma
AU - Jani, Priya
AU - Clayton, Gina M.
AU - Crawford, Frances
AU - White, Janice
AU - Montoya, Alana
AU - Power, Karen
AU - Allen, Todd M.
AU - Streeck, Hendrik
AU - Kaufmann, Daniel E.
AU - Picker, Louis
AU - Kappler, John W.
AU - Walker, Bruce D.
PY - 2016/10/18
Y1 - 2016/10/18
N2 - CD8+ T cell recognition of virus-infected cells is characteristically restricted by major histocompatibility complex (MHC) class I, although rare examples of MHC class II restriction have been reported in Cd4-deficient mice and a macaque SIV vaccine trial using a recombinant cytomegalovirus vector. Here, we demonstrate the presence of human leukocyte antigen (HLA) class II-restricted CD8+ T cell responses with antiviral properties in a small subset of HIV-infected individuals. In these individuals, T cell receptor β (TCRβ) analysis revealed that class II-restricted CD8+ T cells underwent clonal expansion and mediated killing of HIV-infected cells. In one case, these cells comprised 12% of circulating CD8+ T cells, and TCRα analysis revealed two distinct co-expressed TCRα chains, with only one contributing to binding of the class II HLA-peptide complex. These data indicate that class II-restricted CD8+ T cell responses can exist in a chronic human viral infection, and may contribute to immune control.
AB - CD8+ T cell recognition of virus-infected cells is characteristically restricted by major histocompatibility complex (MHC) class I, although rare examples of MHC class II restriction have been reported in Cd4-deficient mice and a macaque SIV vaccine trial using a recombinant cytomegalovirus vector. Here, we demonstrate the presence of human leukocyte antigen (HLA) class II-restricted CD8+ T cell responses with antiviral properties in a small subset of HIV-infected individuals. In these individuals, T cell receptor β (TCRβ) analysis revealed that class II-restricted CD8+ T cells underwent clonal expansion and mediated killing of HIV-infected cells. In one case, these cells comprised 12% of circulating CD8+ T cells, and TCRα analysis revealed two distinct co-expressed TCRα chains, with only one contributing to binding of the class II HLA-peptide complex. These data indicate that class II-restricted CD8+ T cell responses can exist in a chronic human viral infection, and may contribute to immune control.
KW - CD8 T cells
KW - HIV
KW - HLA
KW - MHC class II
KW - TCR
KW - vaccines
UR - http://www.scopus.com/inward/record.url?scp=84994884814&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84994884814&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2016.09.015
DO - 10.1016/j.immuni.2016.09.015
M3 - Article
C2 - 27760342
AN - SCOPUS:84994884814
VL - 45
SP - 917
EP - 930
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 4
ER -