Comparison of the capacity of murine and human class I MHC molecules to stimulate T cell activation

In general, the human CD8 molecule is expressed on T cells specific for HLA class I molecules. Studies designed to delineate the function and to define the ligand of the CD8 molecule have been complicated by the fact that the presumptive ligand for CD8 is on the HLA class I molecule, the same molecule encoding the ligand for the antigen-specific T cell receptor. The ability to express genes in cells other than their natural host has produced a new technology with which to approach CD8 functional studies. The insertion of a cDNA clone for CD8 in a defective retroviral vector has allowed the transfer of CD8 by infection with the resulting defective retrovirus. CD8 was then expressed in an HLA class II-specific T cell, thus separating the ligand requirements of the TCR and CD8. By this approach, the human CD8 molecule was expressed in a murine T cell hybridoma specific for human class II antigens. The resulting CD8+ hybridomas demonstrated a 10-fold increase in IL-2 production over the parent cell line when stimulated with JY, a human B lymphoblastoid cell line expressing both class I and II HLA antigens, demonstrating that expression of CD8 increases T cell activation. mAbs directed against the CD8 molecule inhibited the response of CD8+ hybridomas to JY, supporting the conclusion that the CD8 molecule was fractional. The role of CD8 as a receptor for class I MHC antigens was addressed by stimulation with a cell line expressing HLA-DR antigens, but lacking the expression of HLA class I antigens (Daudi). Stimulation of the CD8+ hybridomas by Daudi did not result in increased IL-2 production. The response to Daudi was unaltered by the addition of anti-CD8 mAb, in contrast to the ability of anti-CD8 mAb to block JY stimulation. Furthermore, mAbs directed against the class I antigens present on JY cells were able to block the enhanced response of the CD8+ hybridomas to JY. These data support the hypothesis that HLA class I molecules are the ligands involved in the CD8-dependent enhancement of T cell activation.

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The CD43 130-kD peripheral T-cell activation antigen is downregulated in thymic positive selection

Blood ◽

10.1182/blood.v88.5.1725.1725 ◽

1996 ◽

Vol 88 (5) ◽

pp. 1725-1732 ◽

Cited By ~ 30

Author(s):

LG Ellies ◽

W Tao ◽

W Fellinger ◽

HS Teh ◽

HJ Ziltener

Keyword(s):

T Cells ◽

T Cell ◽

Positive Selection ◽

T Cell Activation ◽

Cell Activation ◽

Class Ii ◽

Class I ◽

Double Positive ◽

Mhc Molecules ◽

Activation Antigen

Abstract Specific glycoforms of CD43, the major O-glycosylated cell-surface protein on T lymphocytes, can affect cell adhesion according to the types of carbohydrate side chains carried. In the peripheral immune system, CD43 130 kD, which carries core 2 O-glycan structures on its surface, is an activation antigen expressed on both CD4 and CD8 single- positive (SP) T cells. We have previously shown that the 115-kD resting and 130-kD activation glycoforms of murine CD43 are differentially regulated on peripheral SP T cells. In this study, we used transgenic mice expressing T-cell receptors (TCRs) specific for antigens presented by class I and class II major histocompatibility complex (MHC) molecules to determine whether CD43 glycoforms are involved in thymocyte differentiation. Positive selection in these mice results in an increase in the production of CD8 and CD4 SP T cells, respectively, which express the transgenic TCR. Positive selection is also accompanied by the upregulation of TCR, CD69, and CD5. Using these markers to define stages of thymocyte maturation, we found that CD43 130 kD was downregulated in the positive selection of CD4 CD8 double- positive thymocytes expressing a class I but not class II MHC- restricted TCR. These data suggest that core 2 glycosyltransferase (C2GnT) modulated expression of CD43 glycoforms may be involved in thymic selection events.

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The CD43 130-kD peripheral T-cell activation antigen is downregulated in thymic positive selection

Blood ◽

10.1182/blood.v88.5.1725.bloodjournal8851725 ◽

1996 ◽

Vol 88 (5) ◽

pp. 1725-1732 ◽

Cited By ~ 1

Author(s):

LG Ellies ◽

W Tao ◽

W Fellinger ◽

HS Teh ◽

HJ Ziltener

Keyword(s):

T Cells ◽

T Cell ◽

Positive Selection ◽

T Cell Activation ◽

Cell Activation ◽

Class Ii ◽

Class I ◽

Double Positive ◽

Mhc Molecules ◽

Activation Antigen

Specific glycoforms of CD43, the major O-glycosylated cell-surface protein on T lymphocytes, can affect cell adhesion according to the types of carbohydrate side chains carried. In the peripheral immune system, CD43 130 kD, which carries core 2 O-glycan structures on its surface, is an activation antigen expressed on both CD4 and CD8 single- positive (SP) T cells. We have previously shown that the 115-kD resting and 130-kD activation glycoforms of murine CD43 are differentially regulated on peripheral SP T cells. In this study, we used transgenic mice expressing T-cell receptors (TCRs) specific for antigens presented by class I and class II major histocompatibility complex (MHC) molecules to determine whether CD43 glycoforms are involved in thymocyte differentiation. Positive selection in these mice results in an increase in the production of CD8 and CD4 SP T cells, respectively, which express the transgenic TCR. Positive selection is also accompanied by the upregulation of TCR, CD69, and CD5. Using these markers to define stages of thymocyte maturation, we found that CD43 130 kD was downregulated in the positive selection of CD4 CD8 double- positive thymocytes expressing a class I but not class II MHC- restricted TCR. These data suggest that core 2 glycosyltransferase (C2GnT) modulated expression of CD43 glycoforms may be involved in thymic selection events.

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Faculty Opinions recommendation of Invariant chain as a vehicle to load antigenic peptides on human MHC class I for cytotoxic T-cell activation.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718194774.793488232 ◽

2013 ◽

Author(s):

Tim Elliott ◽

Andy van Hateren ◽

Edd James

Keyword(s):

T Cell ◽

Mhc Class I ◽

T Cell Activation ◽

Cell Activation ◽

Class I ◽

Cytotoxic T Cell ◽

Invariant Chain ◽

Antigenic Peptides

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Self–class I MHC molecules support survival of naive CD8 T cells, but depress their functional sensitivity through regulation of CD8 expression levels

Journal of Experimental Medicine ◽

10.1084/jem.20082553 ◽

2009 ◽

Vol 206 (10) ◽

pp. 2253-2269 ◽

Cited By ~ 53

Author(s):

Kensuke Takada ◽

Stephen C. Jameson

Keyword(s):

T Cells ◽

T Cell ◽

Cell Survival ◽

Cd8 T Cells ◽

Cd8 T Cell ◽

Class I ◽

Class I Mhc ◽

Mhc Molecules ◽

T Cell Survival ◽

And Function

Previous studies have suggested that naive CD8 T cells require self-peptide–major histocompatability complex (MHC) complexes for maintenance. However, interpretation of such studies is complicated because of the involvement of lymphopenic animals, as lymphopenia drastically alters naive T cell homeostasis and function. In this study, we explored naive CD8 T cell survival and function in nonlymphopenic conditions by using bone marrow chimeric donors and hosts in which class I MHC expression is absent or limited to radiosensitive versus radioresistant cells. We found that long-term survival of naive CD8 T cells (but not CD4 T cells) was impaired in the absence of class I MHC. However, distinct from this effect, class I MHC deprivation also enhanced naive CD8 T cell responsiveness to low-affinity (but not high-affinity) peptide–MHC ligands. We found that this improved sensitivity was a consequence of up-regulated CD8 levels, which was mediated through a transcriptional mechanism. Hence, our data suggest that, in a nonlymphopenic setting, self-class I MHC molecules support CD8 T cell survival, but that these interactions also attenuate naive T cell sensitivity by dynamic tuning of CD8 levels.

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