Impact of antigen presentation on TCR modulation and cytokine release: Implications for detection and sorting of antigen-specific CD8+ T cells using HLA-A2 wild-type or HLA-A2 mutant tetrameric complexes

Elke Jäger, Russell Salter, Chiara Castelli, Hanni Höhn, Kirsten Freitag, Julia Karbach, Claudia Neukirch, Antje Necker, Alexander Knuth, Markus J. Maeurer

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Soluble MHC class I molecules loaded with antigenic peptides are available either to detect and to enumerate or, alternatively, to sort and expand MHC class I-restricted and peptide-reactive T cells. A defined number of MHC class I/peptide complexes can now be implemented to measure T cell responses induced upon Ag-specific stimulation, including CD3/CD8/ζ-chain down-regulation, pattern, and quantity of cytokine secretion. As a paradigm, we analyzed the reactivity of a Melan-A/MART-1-specific and HLA-A2-restricted CD8+ T cell clone to either soluble or solid-phase presented peptides, including the naturally processed and presented Melan-A/MART-1 peptide AAGIGILTV or the peptide analog ELAGIGILTV presented either by the HLA-A2 wild-type (wt) or mutant (alanine→valine aa 245) MHC class I molecule, which reduces engagement of the CD8 molecule with the HLA-A2 heavy chain. Soluble MHC class I complexes were used as either monomeric or tetrameric complexes. Soluble monomeric MHC class I complexes, loaded with the Melan-A/MART-1 peptide, resulted in CD3/CD8 and TCR ζ-chain down-regulation, but did not induce measurable cytokine release. In general, differences pertaining to CD3/CD8/ζ-chain regulation and cytokine release, including IL-2, IFN-γ, and GM-CSF, were associated with 1) the format of Ag presentation (monomeric vs tetrameric MHC class I complexes), 2) wt vs mutant HLA-A2 molecules, and 3) the target Ag (wt vs analog peptide). These differences are to be considered if T cells are exposed to recombinant MHC class I Ags loaded with peptides implemented for detection, activation, or sorting of Ag-specific T cells.

Original languageEnglish
Pages (from-to)2766-2772
Number of pages7
JournalJournal of Immunology
Volume168
Issue number6
Publication statusPublished - Mar 15 2002

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CD8 Antigens
HLA-A2 Antigen
Antigen Presentation
Cytokines
T-Lymphocytes
Peptides
MART-1 Antigen
Down-Regulation
Peptide T
Granulocyte-Macrophage Colony-Stimulating Factor
Interleukin-2
Clone Cells

ASJC Scopus subject areas

  • Immunology

Cite this

Impact of antigen presentation on TCR modulation and cytokine release : Implications for detection and sorting of antigen-specific CD8+ T cells using HLA-A2 wild-type or HLA-A2 mutant tetrameric complexes. / Jäger, Elke; Salter, Russell; Castelli, Chiara; Höhn, Hanni; Freitag, Kirsten; Karbach, Julia; Neukirch, Claudia; Necker, Antje; Knuth, Alexander; Maeurer, Markus J.

In: Journal of Immunology, Vol. 168, No. 6, 15.03.2002, p. 2766-2772.

Research output: Contribution to journalArticle

Jäger, Elke ; Salter, Russell ; Castelli, Chiara ; Höhn, Hanni ; Freitag, Kirsten ; Karbach, Julia ; Neukirch, Claudia ; Necker, Antje ; Knuth, Alexander ; Maeurer, Markus J. / Impact of antigen presentation on TCR modulation and cytokine release : Implications for detection and sorting of antigen-specific CD8+ T cells using HLA-A2 wild-type or HLA-A2 mutant tetrameric complexes. In: Journal of Immunology. 2002 ; Vol. 168, No. 6. pp. 2766-2772.
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