scholarly journals Expression and function of CD8 in a murine T cell hybridoma.

1987 ◽  
Vol 166 (6) ◽  
pp. 1747-1757 ◽  
Author(s):  
S E Ratnofsky ◽  
A Peterson ◽  
J L Greenstein ◽  
S J Burakoff
Keyword(s):  
T Cell ◽  
Cell Line ◽  
T Cell Activation ◽  
Cell Activation ◽  
Hla Class I ◽  
Class Ii ◽  
Class I ◽  
Parent Cell ◽  
Class I Mhc ◽  
Hla Class I Molecules

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.

scholarly journals γδ T cell activation or anergy during infections: the role of nonpeptidic TCR ligands and HLA class I molecules

1997 ◽  
Vol 62 (3) ◽  
pp. 287-291 ◽  
Author(s):  
Fabrizio Poccia ◽  
Miroslav Malkovsky ◽  
Marie Lise Gougeon ◽  
Marc Bonneville ◽  
Miguel Lopez-Botet ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Hla Class I ◽  
Class I ◽  
Γδ T Cell ◽  
Hla Class I Molecules

scholarly journals Antigen identification for HLA class I– and HLA class II–restricted T cell receptors using cytokine-capturing antigen-presenting cells

2021 ◽  
Vol 6 (55) ◽  
pp. eabf4001
Author(s):  
Mark N. Lee ◽  
Matthew Meyerson
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Human Leukocyte ◽  
Antigen Presenting Cells ◽  
Hla Class I ◽  
Class Ii ◽  
Class I ◽  
Identification System ◽  
Antigen Presenting

A major limitation to understanding the associations of human leukocyte antigen (HLA) and CD8+ and CD4+ T cell receptor (TCR) genes with disease pathophysiology is the technological barrier of identifying which HLA molecules, epitopes, and TCRs form functional complexes. Here, we present a high-throughput epitope identification system that combines capture of T cell–secreted cytokines by barcoded antigen-presenting cells (APCs), cell sorting, and next-generation sequencing to identify class I– and class II–restricted epitopes starting from highly complex peptide-encoding oligonucleotide pools. We engineered APCs to express anti-cytokine antibodies, a library of DNA-encoded peptides, and multiple HLA class I or II molecules. We demonstrate that these engineered APCs link T cell activation–dependent cytokines with the DNA that encodes the presented peptide. We validated this technology by showing that we could select known targets of viral epitope–, neoepitope-, and autoimmune epitope–specific TCRs, starting from mixtures of peptide-encoding oligonucleotides. Then, starting from 10 TCRβ sequences that are found commonly in humans but lack known targets, we identified seven CD8+ or CD4+ TCR-targeted epitopes encoded by the human cytomegalovirus (CMV) genome. These included known epitopes, as well as a class I and a class II CMV epitope that have not been previously described. Thus, our cytokine capture–based assay makes use of a signal secreted by both CD8+ and CD4+ T cells and allows pooled screening of thousands of encoded peptides to enable epitope discovery for orphan TCRs. Our technology may enable identification of HLA-epitope-TCR complexes relevant to disease control, etiology, or treatment.

scholarly journals Loss of CD8 and TCR binding to Class I MHC ligands following T cell activation

2005 ◽  
Vol 17 (12) ◽  
pp. 1607-1617 ◽  
Author(s):  
Charlly Kao ◽  
Mark A. Daniels ◽  
Stephen C. Jameson
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Class I ◽  
Class I Mhc ◽  
Mhc Ligands

CD4 function in thymocyte differentiation and T cell activation

1993 ◽  
Vol 342 (1299) ◽  
pp. 25-34 ◽  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mhc Class Ii ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cell Subset ◽  
Class Ii ◽  
Class I ◽  
Double Positive

The ectodomains of the T cell surface glycoproteins CD4 and CD8 bind to membrane-proximal domains of MHC class II and class I molecules, respectively, while both cytoplasmic domains interact with the protein tyrosine kinase (PTK) p56 lck (lck) through a shared cysteine-containing motif. Function of CD4 and CD8 requires their binding to the same MHC molecule as that recognized by the T cell antigen receptor (TCR). In vitro studies indicate that CD4-associated lck functions even in the absence of kinase activity. In vivo experiments show that, whereas helper T cell development is impaired in CD4-deficient mice, high level expression of a transgenic CD4 that cannot bind lck rescues development of this T cell subset. These studies suggest that CD4 is an adhesion molecule whose localization is regulated through protein-protein interactions of the associated PTK and whose function is to increase the stability of the TCR signalling complex by binding to the relevant MHC. The function of CD4 in development has been further studied in the context of how double positive (CD4+ CD8+ ) thymocytes mature into either CD4 + T cells with helper function and TCR specificity for class II or into CD8 + T cells with cytotoxic function and specificity for class I. Studies using CD4- transgenic mice indicate that development of single positive T cells involves stochastic downregulation of either CD4 or CD8, coupled to activation of a cytotoxic or helper program, respectively, and subsequent selection based on the ability of the TCR and remaining coreceptor to engage the same MHC molecule.

HLAs, TCRs, and KIRs, a Triumvirate of Human Cell-Mediated Immunity

2020 ◽  
Vol 89 (1) ◽  
pp. 717-739 ◽  
Author(s):  
Zakia Djaoud ◽  
Peter Parham
Keyword(s):  
T Cells ◽  
T Cell ◽  
Nk Cells ◽  
T Cell Receptors ◽  
Hla Class I ◽  
Class Ii ◽  
Class I ◽  
Antigenic Specificity ◽  
Class I Mhc ◽  
Cell Receptors

In all human cells, human leukocyte antigen (HLA) class I glycoproteins assemble with a peptide and take it to the cell surface for surveillance by lymphocytes. These include natural killer (NK) cells and γδ T cells of innate immunity and αβ T cells of adaptive immunity. In healthy cells, the presented peptides derive from human proteins, to which lymphocytes are tolerant. In pathogen-infected cells, HLA class I expression is perturbed. Reduced HLA class I expression is detected by KIR and CD94:NKG2A receptors of NK cells. Almost any change in peptide presentation can be detected by αβ CD8+ T cells. In responding to extracellular pathogens, HLA class II glycoproteins, expressed by specialized antigen-presenting cells, present peptides to αβ CD4+ T cells. In comparison to the families of major histocompatibility complex (MHC) class I, MHC class II and αβ T cell receptors, the antigenic specificity of the γδ T cell receptors is incompletely understood.

Sign in / Sign up

Export Citation Format

Share Document