Direct presentation regulates the magnitude of the CD8+ T cell response to cell-associated antigen through prolonged T cell proliferation

Angela M. Tatum, Alan M. Watson, Todd Schell

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The magnitude and complexity of Ag-specific CD8+ T cell responses is determined by intrinsic properties of the immune system and extrinsic factors, such as vaccination. We evaluated mechanisms that regulate the CD8+ T cell response to two distinct determinants derived from the same protein Ag, SV40 T Ag (T Ag), following immunization of C57BL/6 mice with T Ag-transformed cells. The results show that direct presentation of T cell determinants by T Ag-transformed cells regulates the magnitude of the CD8 + T cell response in vivo but not the immunodominance hierarchy. The immunodominance hierarchy was reversed in a dose-dependent manner by addition of excess naive T cells targeting the subdominant determinant. However, T cell competition played only a minor role in limiting T cell accumulation under physiological conditions. We found that the magnitude of the T cell response was regulated by the ability of T Ag-transformed cells to directly present the T Ag determinants. The hierarchy of the CD8+ T cell response was maintained when Ag presentation in vivo was restricted to cross-presentation, but the presence of T Ag-transformed cells capable of direct presentation dramatically enhanced T cell accumulation at the peak of the response. This enhancement was due to a prolonged period of T cell proliferation, resulting in a delay in T cell contraction. Our findings reveal that direct presentation by nonprofessional APCs can dramatically enhance accumulation of CD8+ T cells during the primary response, revealing a potential strategy to enhance vaccination approaches.

Original languageEnglish (US)
Pages (from-to)2763-2772
Number of pages10
JournalJournal of Immunology
Volume185
Issue number5
DOIs
StatePublished - Sep 1 2010

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Cell Proliferation
T-Lymphocytes
Antigens
Vaccination
Cross-Priming
Polyomavirus Transforming Antigens
Inbred C57BL Mouse
Immune System
Immunization

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

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abstract = "The magnitude and complexity of Ag-specific CD8+ T cell responses is determined by intrinsic properties of the immune system and extrinsic factors, such as vaccination. We evaluated mechanisms that regulate the CD8+ T cell response to two distinct determinants derived from the same protein Ag, SV40 T Ag (T Ag), following immunization of C57BL/6 mice with T Ag-transformed cells. The results show that direct presentation of T cell determinants by T Ag-transformed cells regulates the magnitude of the CD8 + T cell response in vivo but not the immunodominance hierarchy. The immunodominance hierarchy was reversed in a dose-dependent manner by addition of excess naive T cells targeting the subdominant determinant. However, T cell competition played only a minor role in limiting T cell accumulation under physiological conditions. We found that the magnitude of the T cell response was regulated by the ability of T Ag-transformed cells to directly present the T Ag determinants. The hierarchy of the CD8+ T cell response was maintained when Ag presentation in vivo was restricted to cross-presentation, but the presence of T Ag-transformed cells capable of direct presentation dramatically enhanced T cell accumulation at the peak of the response. This enhancement was due to a prolonged period of T cell proliferation, resulting in a delay in T cell contraction. Our findings reveal that direct presentation by nonprofessional APCs can dramatically enhance accumulation of CD8+ T cells during the primary response, revealing a potential strategy to enhance vaccination approaches.",
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Direct presentation regulates the magnitude of the CD8+ T cell response to cell-associated antigen through prolonged T cell proliferation. / Tatum, Angela M.; Watson, Alan M.; Schell, Todd.

In: Journal of Immunology, Vol. 185, No. 5, 01.09.2010, p. 2763-2772.

Research output: Contribution to journalArticle

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