Factors affecting the efficiency of CD8+ T cell cross-priming with exogenous antigens

H. T. Maecker, S. A. Ghanekar, M. A. Suni, X. S. He, Louis Picker, V. C. Maino

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Processing of exogenous protein Ags by APC leads predominantly to presentation of peptides on class II MHC and, thus, stimulation of CD4+ T cell responses. However, "cross-priming" can also occur, whereby peptides derived from exogenous Ags become displayed on class I MHC molecules and stimulate CD8+ T cell responses. We compared the efficiency of cross-priming with exogenous proteins to use of peptide Ags in human whole blood using a flow cytometry assay to detect T cell intracellular cytokine production. CD8+ T cell responses to whole CMV proteins were poorly detected (compared with peptide responses) in most CMV-seropositive donors. Such responses could be increased by using higher doses of Ag than were required to achieve maximal CD4+ T cell responses. A minority of donors displayed significantly more efficient CD8+ T cell responses to whole protein, even at low Ag doses. These responses were MHC class I-restricted and dependent upon proteosomal processing, indicating that they were indeed due to cross-priming. The ability to efficiently cross-prime was not a function of the number of dendritic cells in the donor's blood. Neither supplementation of freshly isolated dendritic cells nor use of cultured, Ag-pulsed dendritic cells could significantly boost CD8 responses to whole-protein Ags in poorly cross-priming donors. Interestingly, freshly isolated monocytes performed almost as well as dendritic cells in inducing CD8 responses via cross-priming. In conclusion, the efficiency of cross-priming appears to be poor in most donors and is dependent upon properties of the individual's APC and/or T cell repertoire. It remains unknown whether cross-priming ability translates into any clinical advantage in ability to induce CD8+ T cell responses to foreign Ags.

Original languageEnglish (US)
Pages (from-to)7268-7275
Number of pages8
JournalJournal of Immunology
Volume166
Issue number12
StatePublished - Jun 15 2001
Externally publishedYes

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Cross-Priming
T-Lymphocytes
Antigens
Dendritic Cells
Tissue Donors
Peptides
Proteins
Blood Donors
Monocytes
Flow Cytometry
Cytokines

ASJC Scopus subject areas

  • Immunology

Cite this

Maecker, H. T., Ghanekar, S. A., Suni, M. A., He, X. S., Picker, L., & Maino, V. C. (2001). Factors affecting the efficiency of CD8+ T cell cross-priming with exogenous antigens. Journal of Immunology, 166(12), 7268-7275.

Factors affecting the efficiency of CD8+ T cell cross-priming with exogenous antigens. / Maecker, H. T.; Ghanekar, S. A.; Suni, M. A.; He, X. S.; Picker, Louis; Maino, V. C.

In: Journal of Immunology, Vol. 166, No. 12, 15.06.2001, p. 7268-7275.

Research output: Contribution to journalArticle

Maecker, HT, Ghanekar, SA, Suni, MA, He, XS, Picker, L & Maino, VC 2001, 'Factors affecting the efficiency of CD8+ T cell cross-priming with exogenous antigens', Journal of Immunology, vol. 166, no. 12, pp. 7268-7275.
Maecker HT, Ghanekar SA, Suni MA, He XS, Picker L, Maino VC. Factors affecting the efficiency of CD8+ T cell cross-priming with exogenous antigens. Journal of Immunology. 2001 Jun 15;166(12):7268-7275.
Maecker, H. T. ; Ghanekar, S. A. ; Suni, M. A. ; He, X. S. ; Picker, Louis ; Maino, V. C. / Factors affecting the efficiency of CD8+ T cell cross-priming with exogenous antigens. In: Journal of Immunology. 2001 ; Vol. 166, No. 12. pp. 7268-7275.
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