Unknown

Dataset Information

0

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


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.

SUBMITTER: Tatum AM 

PROVIDER: S-EPMC2924944 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Tatum Angela M AM   Watson Alan M AM   Schell Todd D TD  

Journal of immunology (Baltimore, Md. : 1950) 20100726 5


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  ...[more]

Similar Datasets

| S-EPMC4305442 | biostudies-literature
| S-EPMC2865532 | biostudies-literature
| S-EPMC5940548 | biostudies-literature
| S-EPMC6204794 | biostudies-literature
| S-EPMC5520673 | biostudies-literature
| S-EPMC2646168 | biostudies-literature
| S-EPMC4113940 | biostudies-literature
| S-EPMC7172366 | biostudies-literature
| S-EPMC2820535 | biostudies-literature
| S-EPMC3100200 | biostudies-literature