Dendritic cell vaccination induces cross-reactive cytotoxic T lymphocytes specific for wild-type and natural variant human immunodeficiency virus type 1 epitopes in HLA-A*0201/Kbtransgenic mice

Ussama M. Abdel-Motal, Randall Friedline, Brian Poligone, Rebecca R. Pogue-Caley, Jeffrey A. Frelinger, Roland Tisch

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Dendritic cells (DC) are highly efficient at inducing primary T cell responses. Consequently, DC are being investigated for their potential to prevent and/or treat human immunodeficiency virus type 1 (HIV-1) infection. In the current study, we examined the capacity of DC to elicit CD8+cytotoxic T lymphocyte (CTL) reactivity against an HLA-A*0201-restricted HIV-1 reverse transcriptase (pol) epitope (residues 476-484) and two naturally occurring variants. Previous work demonstrated that the wild-type pol epitope is recognized by CTLs from HIV-1-infected individuals, whereas the variant pol epitopes are not, despite binding to HLA-A*0201. In agreement with these observations, parenteral administration of wild-type pol peptide induced HLA-A*0201-restricted CTL activity in A2Kbtransgenic mice. In contrast, similar treatment with the two variant pol peptides failed to stimulate CTL reactivity, and this lack of immunogenicity correlated with reduced peptide:HLA-A*0201 complex stability. However, CTL responses were induced in A2Kbtransgenic mice upon adoptive transfer of syngeneic bone marrow DC pulsed with the variant pol peptides. Furthermore, DC pulsed with the wild-type pol peptide elicited CTLs that cross-reacted with the variant pol epitopes. These results demonstrate that DC effectively expand the T cell repertoire of a given epitope to include cross-reactive T cell clonotypes. Accordingly, DC vaccination may aid in immune recognition of HIV-1 escape variants by broadening the T cell response.

Original languageEnglish
Pages (from-to)51-58
Number of pages8
JournalClinical Immunology
Volume101
Issue number1
DOIs
Publication statusPublished - 2001
Externally publishedYes

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Cytotoxic T-Lymphocytes
Dendritic Cells
HIV-1
Epitopes
Vaccination
Peptides
T-Lymphocytes
Adoptive Transfer
Virus Diseases
HLA-A*02:01 antigen
Bone Marrow Cells

Keywords

  • CTL
  • Dendritic cell
  • HIV
  • Vaccines

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Dendritic cell vaccination induces cross-reactive cytotoxic T lymphocytes specific for wild-type and natural variant human immunodeficiency virus type 1 epitopes in HLA-A*0201/Kbtransgenic mice. / Abdel-Motal, Ussama M.; Friedline, Randall; Poligone, Brian; Pogue-Caley, Rebecca R.; Frelinger, Jeffrey A.; Tisch, Roland.

In: Clinical Immunology, Vol. 101, No. 1, 2001, p. 51-58.

Research output: Contribution to journalArticle

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