Antiviral CD8+ T Cells Restricted by Human Leukocyte Antigen Class II Exist during Natural HIV Infection and Exhibit Clonal Expansion

Srinika Ranasinghe, Pedro A. Lamothe, Damien Z. Soghoian, Samuel W. Kazer, Michael B. Cole, Alex K. Shalek, Nir Yosef, R. Brad Jones, Faith Donaghey, Chioma Nwonu, Priya Jani, Gina M. Clayton, Frances Crawford, Janice White, Alana Montoya, Karen Power, Todd M. Allen, Hendrik Streeck, Daniel E. Kaufmann, Louis Picker & 2 others John W. Kappler, Bruce D. Walker

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)917-930
Number of pages14
JournalImmunity
Volume45
Issue number4
DOIs
StatePublished - Oct 18 2016

Fingerprint

HLA Antigens
HIV Infections
Antiviral Agents
Major Histocompatibility Complex
T-Lymphocytes
SAIDS Vaccines
HIV
HLA-D Antigens
Macaca
Virus Diseases
Cytomegalovirus
Viruses
Peptides

Keywords

  • CD8 T cells
  • HIV
  • HLA
  • MHC class II
  • TCR
  • vaccines

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Ranasinghe, S., Lamothe, P. A., Soghoian, D. Z., Kazer, S. W., Cole, M. B., Shalek, A. K., ... Walker, B. D. (2016). Antiviral CD8+ T Cells Restricted by Human Leukocyte Antigen Class II Exist during Natural HIV Infection and Exhibit Clonal Expansion. Immunity, 45(4), 917-930. https://doi.org/10.1016/j.immuni.2016.09.015

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 journalArticle

Ranasinghe, S, Lamothe, PA, Soghoian, DZ, Kazer, SW, Cole, MB, Shalek, AK, Yosef, N, Jones, RB, Donaghey, F, Nwonu, C, Jani, P, Clayton, GM, Crawford, F, White, J, Montoya, A, Power, K, Allen, TM, Streeck, H, Kaufmann, DE, Picker, L, Kappler, JW & Walker, BD 2016, 'Antiviral CD8+ T Cells Restricted by Human Leukocyte Antigen Class II Exist during Natural HIV Infection and Exhibit Clonal Expansion', Immunity, vol. 45, no. 4, pp. 917-930. https://doi.org/10.1016/j.immuni.2016.09.015
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. / Antiviral CD8+ T Cells Restricted by Human Leukocyte Antigen Class II Exist during Natural HIV Infection and Exhibit Clonal Expansion. In: Immunity. 2016 ; Vol. 45, No. 4. pp. 917-930.
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