scholarly journals Highly lytic CD8+, alpha beta T-cell receptor cytotoxic T cells with major histocompatibility complex (MHC) class I antigen-directed cytotoxicity in beta 2-microglobulin, MHC class I-deficient mice.

1993 ◽  
Vol 90 (7) ◽  
pp. 2837-2841 ◽  
Author(s):  
S. Apasov ◽  
M. Sitkovsky
Keyword(s):  
Mhc Class I ◽  
T Cell Receptor ◽  
Cytotoxic T Cells ◽  
Cell Receptor ◽  
Class I ◽  
Histocompatibility Complex ◽  
Mhc Class I Antigen ◽  
Alpha Beta ◽  
Beta 2 Microglobulin ◽  
Deficient Mice

scholarly journals Major histocompatibility complex class I related molecules control the development of CD4+8- and CD4-8- subsets of natural killer 1.1+ T cell receptor-alpha/beta+ cells in the liver of mice.

1994 ◽  
Vol 180 (2) ◽  
pp. 699-704 ◽  
Author(s):  
T Ohteki ◽  
H R MacDonald
Keyword(s):  
T Cell ◽  
Beta Cells ◽  
Mhc Class I ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Class I ◽  
Histocompatibility Complex ◽  
Alpha Beta ◽  
Beta 2 Microglobulin ◽  
Deficient Mice

Normal mouse liver contains prominent subsets of CD4+8- and CD4-8- T cell receptor (TCR)-alpha/beta+ cells with intermediate TCR levels. We show here that these cells express the natural killer (NK)1.1 surface antigen and have a restricted TCRV beta repertoire that is highly skewed to V beta 7 and V beta 8. Surprisingly, both CD4+8- and CD4-8- subsets of NK1.1+TCR-alpha/beta+ cells are absent in the liver of beta 2-microglobulin deficient mice, which do not express major histocompatibility complex (MHC) class I or "class I-like" molecules. Analysis of reciprocal radiation bone marrow chimeras established with beta 2-microglobulin deficient and wild-type mice demonstrates that MHC class I expression on radiosensitive (presumably hematopoietic) cells is required for the development of NK1.1+TCR-alpha/beta+ cells in the liver. In the liver of MHC class II deficient mice, the CD4+8- and CD4-8- subsets of NK1.1+TCR-alpha/beta+ cells develop normally. Collectively our data suggest that NK1.1+TCR-alpha/beta+ cells in liver require interaction with a MHC class I-related ligand on hematopoietic cells for their development. This unusual property of liver T cells is shared by a subset of CD4-8-NK1.1+TCR-alpha/beta+ thymocytes, suggesting a common lineage independent of the mainstream of T cell development.

scholarly journals An invariant T cell receptor alpha chain is used by a unique subset of major histocompatibility complex class I-specific CD4+ and CD4-8- T cells in mice and humans.

1994 ◽  
Vol 180 (3) ◽  
pp. 1097-1106 ◽  
Author(s):  
O Lantz ◽  
A Bendelac
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Mhc Class I ◽  
T Cell Receptor ◽  
Cell Subset ◽  
Cell Receptor ◽  
Class I ◽  
T Cell Subset ◽  
Alpha Chain ◽  
Histocompatibility Complex

The mouse thymus contains a mature T cell subset that is distinguishable from the mainstream thymocytes by several characteristics. It is restricted in its usage of T cell receptor (TCR) V beta genes to V beta 8, V beta 7, and V beta 2. Its surface phenotype is that of activated/memory cells. It carries the natural killer NK1.1 surface marker. Furthermore, though it consists entirely of CD4+ and CD4-8- cells, its selection in the thymus depends solely upon major histocompatibility complex (MHC) class I expression by cells of hematopoietic origin. Forced persistence of CD8, in fact, imparts negative selection. Here, we have studied the TCR repertoire of this subset and found that, whereas the beta chain V-D-J junctions are quite variable, a single invariant alpha chain V alpha 14-J281 is used by a majority of the TCRs. This surprisingly restricted usage of the V alpha 14-J281 alpha chain is dependent on MHC class I expression, but independent of the MHC haplotype. In humans, a similar unusual population including CD4-8- cells can also be found that uses a strikingly homologous, invariant alpha chain V alpha 24-JQ. Thus, this unique V alpha-J alpha combination has been conserved in both species, conferring specificity to some shared nonpolymorphic MHC class I/peptide self-ligand(s). This implies that the T cell subset that it defines has a specialized and important role, perhaps related to its unique ability to secrete a large set of lymphokines including interleukin 4, upon primary stimulation in vitro and in vivo.

scholarly journals CD4-CD8- T cell receptor alpha beta T cells: generation of an in vitro major histocompatibility complex class I specific cytotoxic T lymphocyte response and allogeneic tumor rejection.

1991 ◽  
Vol 174 (1) ◽  
pp. 193-201 ◽  
Author(s):  
M Mieno ◽  
R Suto ◽  
Y Obata ◽  
H Udono ◽  
T Takahashi ◽  
...  
Keyword(s):  
T Cell Receptor ◽  
Cell Receptor ◽  
Tumor Rejection ◽  
Class I ◽  
Cd4 Cells ◽  
Spleen Cells ◽  
Cd8 Cells ◽  
Histocompatibility Complex ◽  
Alpha Beta

The generation of an in vitro major histocompatibility complex class I specific response of CD4-CD8- T cell receptor (TCR) alpha beta cytotoxic T lymphocytes (CTL) and their allogeneic tumor rejection were investigated. Inocula of BALBRL male 1 were rejected in C57BL/6 (B6) mice treated with minimum essential medium (MEM) (control), anti-L3T4 (CD4) monoclonal antibody (mAb) or anti-Lyt-2.2 (CD8) mAb and CTL against the tumor were generated in vitro. No rejection and no induction of CTL were observed in B6 mice treated with anti-L3T4 (CD4) plus anti-Lyt-2.2 (CD8) mAb. CTL with the classical Thy-1+ CD3+CD4-CD8+ TCR alpha beta phenotype were generated in mixed lymphocyte tumor cell culture (MLTC) spleen cells from B6 mice treated with MEM (control) or anti-L3T4 (CD4) mAb, whereas CTL with an unusual Thy-1+CD3+CD4-CD8- TCR alpha beta phenotype were generated in MLTC spleen cells from anti-Lyt-2.2 (CD8) mAb-treated B6 mice. Both types of CTL were reactive with both H-2Kd and Dd (Ld) class I antigen. These findings suggest that when CD4+ cells were blocked by anti-L3T4 (CD4) mAb, CD8+ CTL mediated rejection, and when CD8+ cells were blocked by anti-Lyt-2.2 (CD8) mAb, CD4+ cells were capable of mediating rejection, although less efficiently than CD8+ cells, by inducing CD4-CD8- TCR alpha beta CTL. The finding that adoptive transfer of CD4 and CD8-depleted MLTC spleen cells, obtained from anti-Lyt-2.2 (CD8) mAb-treated B6 mice that had rejected BALBRL male 1, resulted in rejection of BALBRL male 1 inoculated into B6 nu/nu mice confirmed the above notion. CTL clones with the CD4-CD8- TCR alpha beta phenotype specific for Ld were established.

scholarly journals The V beta complementarity determining region 1 of a major histocompatibility complex (MHC) class I-restricted T cell receptor is involved in the recognition of peptide/MHC I and superantigen/MHC II complex.

1994 ◽  
Vol 179 (4) ◽  
pp. 1087-1097 ◽  
Author(s):  
M Bellio ◽  
Y C Lone ◽  
O de la Calle-Martin ◽  
B Malissen ◽  
J P Abastado ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Mhc Class I ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Class I ◽  
Mhc I ◽  
Mhc Ii ◽  
Histocompatibility Complex ◽  
Complementarity Determining Region

We investigated the role of the complementarity determining region 1 (CDR1) of T cell receptor (TCR) beta chain both in antigen/major histocompatibility complex I (MHC I) and in superantigen (SAg)/MHC II complex recognition. Residues 26 to 31 of the V beta 10 domain of a TCR derived from an H-2Kd-restricted cytotoxic clone were individually changed to alanine, using site-directed mutagenesis, and the mutated TCR beta chains were transfected along with the wild-type TCR alpha chain into a TCR alpha-beta-T hydridoma. These mutations affected antigen/H-2Kd complex recognition, although to a different extent, as estimated by interleukin 2 production. Certain mutations also affected differently the recognition of two Staphylococcal toxins, exfoliative toxin and Staphylococcal enterotoxin C2, presented by HLA-DR1. Whereas mutation of residues D30 or T31 affect the recognition of both toxins, residues T26, L27, and H29 are critical for the recognition of only one of the SAgs. These observations demonstrate the participation of the CDR1 region in the recognition of peptide/MHC class I as well as SAg/MHC II complexes.

scholarly journals Interleukin 7 induces preferential expansion of V beta 8.2+CD4-8- and V beta 8.2+CD4+8- murine thymocytes positively selected by class I molecules.

1994 ◽  
Vol 180 (2) ◽  
pp. 653-661 ◽  
Author(s):  
A Vicari ◽  
M do C de Moraes ◽  
J M Gombert ◽  
M Dy ◽  
C Penit ◽  
...  
Keyword(s):  
Immune Responses ◽  
Culture System ◽  
Cell Receptor ◽  
Class I ◽  
Interleukin 7 ◽  
Tcr Repertoire ◽  
Alpha Beta ◽  
Beta 2 Microglobulin ◽  
Deficient Mice

We analyzed the phenotype and V beta-T cell receptor (TCR) repertoire, together with interleukin 7 receptor (IL-7R) expression in unfractionated thymocytes stimulated in vitro with IL-7. This culture system results in a specific proliferation of mature thymocytes belonging to the CD3+CD4-, CD4+8-, and CD4-8+ subsets. IL-7 induced a preferential expansion of V beta 8.2+CD4-8- and V beta 8.2+CD4-8- thymocytes. This phenomenon is not observed in beta 2-microglobulin-deficient mice, showing that a fraction of CD4+8- thymocytes, enriched in V beta 8.2+ cells, is selected by class I molecules in normal mice, as are a large proportion of CD4-8- alpha beta TCR+ thymocytes. Our findings also establish that IL-7 plays a major role in the expansion of rare thymocyte subsets, which could exert important functions in inflammatory and immune responses.

T-cell-receptor-like antibodies – generation, function and applications

2012 ◽  
Vol 14 ◽  
Author(s):  
Rony Dahan ◽  
Yoram Reiter
Keyword(s):  
T Cell ◽  
Mhc Class I ◽  
T Cell Receptor ◽  
Cytotoxic T Cells ◽  
Membrane Surface ◽  
Cell Receptor ◽  
Class I ◽  
New Class ◽  
Infected Cells ◽  
Peptide Complexes

Tumour and virus-infected cells are recognised by CD8+ cytotoxic T cells that, in response, are activated to eliminate these cells. In order to be activated, the clonotypic T-cell receptor (TCR) needs to encounter a specific peptide antigen presented by the membrane surface major histocompatibility complex (MHC) molecule. Cells that have undergone malignant transformation or viral infection present peptides derived from tumour-associated antigens or viral proteins on their MHC class I molecules. Therefore, disease-specific MHC–peptide complexes are desirable targets for immunotherapeutic approaches. One such approach transforms the unique fine specificity but low intrinsic affinity of TCRs to MHC–peptide complexes into high-affinity soluble antibody molecules endowed with a TCR-like specificity towards tumour or viral epitopes. These antibodies, termed TCR-like antibodies, are being developed as a new class of immunotherapeutics that can target tumour and virus-infected cells and mediate their specific killing. In addition to their therapeutic capabilities, TCR-like antibodies are being developed as diagnostic reagents for cancer and infectious diseases, and serve as valuable research tools for studying MHC class I antigen presentation.

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