Histocompatibility antigen-activated cytotoxic T lymphocytes. I. Estimates of the absolute frequency of killer cells generated in vitro.

Lindahl, Kirsten Fischer; Wilson, Darcy B.

doi:10.1084/jem.145.3.500

Cited by 88 publications

(45 citation statements)

References 9 publications

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“…Adherent islets were then labeled with 5 Ci/well of 51 Cr for 3 h at 37°C. Islets were washed and overlaid with 100 l of medium containing various numbers of T cells from NOD.Rag1…”

Section: Cytotoxicity Assays Using Intact Islets As Targetsmentioning

confidence: 99%

Requirement for Both H-2Db and H-2Kd for the Induction of Diabetes by the Promiscuous CD8+ T Cell Clonotype AI4

Takaki

Lieberman

Holl

et al. 2004

The Journal of Immunology

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The NOD mouse is a model for autoimmune type 1 diabetes in humans. CD8+ T cells are essential for the destruction of the insulin-producing pancreatic β cells characterizing this disease. AI4 is a pathogenic CD8+ T cell clone, isolated from the islets of a 5-wk-old female NOD mouse, which is capable of mediating overt diabetes in the absence of CD4+ T cell help. Recent studies using MHC-congenic NOD mice revealed marked promiscuity of the AI4 TCR, as the selection of this clonotype can be influenced by multiple MHC molecules, including some class II variants. The present work was designed, in part, to determine whether similar promiscuity also characterizes the effector function of mature AI4 CTL. Using splenocyte and bone marrow disease transfer models and in vitro islet-killing assays, we report that efficient recognition and destruction of β cells by AI4 requires the β cells to simultaneously express both H-2Db and H-2Kd class I MHC molecules. The ability of the AI4 TCR to interact with both H-2Db and H-2Kd was confirmed using recombinant peptide libraries. This approach also allowed us to define a mimotope peptide recognized by AI4 in an H-2Db-restricted manner. Using ELISPOT and mimotope/H-2Db tetramer analyses, we demonstrate for the first time that AI4 represents a readily detectable T cell population in the islet infiltrates of prediabetic NOD mice. Our identification of a ligand for AI4-like T cells will facilitate further characterization and manipulation of this pathogenic and promiscuous T cell population.

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“…Adherent islets were then labeled with 5 Ci/well of 51 Cr for 3 h at 37°C. Islets were washed and overlaid with 100 l of medium containing various numbers of T cells from NOD.Rag1…”

Section: Cytotoxicity Assays Using Intact Islets As Targetsmentioning

confidence: 99%

Requirement for Both H-2Db and H-2Kd for the Induction of Diabetes by the Promiscuous CD8+ T Cell Clonotype AI4

Takaki

Lieberman

Holl

et al. 2004

The Journal of Immunology

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“…Up to 10% of T cells recognize foreign MHC class I and class II molecules (8,9). Two models have been proposed to account for the high frequency of alloreactive T cells (reviewed in Ref.…”

mentioning

confidence: 99%

Investigation of Peptide Involvement in T Cell Allorecognition Using Recombinant HLA Class I Multimers

Whitelegg

Oosten²,

Jordan³

et al. 2005

The Journal of Immunology

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Alloreactive T cells are involved in injurious graft rejection and graft-vs-host disease. However, they can also evoke beneficial responses to tumor Ags restricted by foreign MHC molecules. Manipulation of these alloreactivities requires information on the basis of T cell allorecognition. The vigorous T cell response to foreign MHC molecules may arise from peptide-independent recognition of polymorphic residues of foreign MHC molecules or peptide-specific recognition of novel peptides presented by foreign MHC molecules. We investigated CD8+ T cell allorecognition using recombinant HLA class I/peptide complexes. Peptide-specific allorecognition was examined using tetramers of HLA-A*0201 representing five peptides derived from ubiquitously expressed self-proteins that are known to bind endogenously to HLA-A*0201. Distinct subsets of CD8+ T cells specific for each HLA-A*0201/peptide combination were detected within four in vitro-stimulated T cell populations specific for foreign HLA-A*0201. Peptide-independent allorecognition was investigated using artificial Ag-presenting constructs (aAPCs) coated with CD54, CD80, and functional densities of a single HLA-A*0201/peptide combination for four different peptides. None of the four T cell populations specific for foreign HLA-A*0201 were stimulated by the aAPCs, whereas they did produce IFN-γ upon stimulation with cells naturally expressing HLA-A*0201. Thus, aAPCs did not stimulate putative peptide-independent allorestricted T cells. The results show that these alloreactive populations comprise subsets of T cells, each specific for a self-peptide presented by foreign class I molecules, with no evidence of peptide-independent components.

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“…The cell pellets were resuspended on a Vortex mixer, and 50 ftl of assay medium was added to each well. 10,000 labeled target cells were added in 100 ~1 assay medium to each well, and the cultures were centrifuged, incubated for 6 h, and the amount of 51Cr released into the supernate measured, all as previously described (7).…”

mentioning

confidence: 99%

“…Washing media, culture media, and assay media were prepared as described in the accompanying paper (7). Conditioned medium was prepared in batches of 0.5-1 liter at a time.…”

mentioning

confidence: 99%

“…Another EL-4 line obtained from Dr. W. Biddison (Wistar Institute, Philadelphia, Pa.), was maintained in tissue culture. Target cells were prepared and labeled as described (7), except that lower doses ofs~Cr (250/~Ci to 1 mCi) and shorter labeling periods (45 min to 2 h) were used. The labeled target cells were suspended at 105 viable cells/ml of assay medium.…”

mentioning

confidence: 99%

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Histocompatibility antigen-activated cytotoxic T lymphocytes. II. Estimates of the frequency and specificity of precursors.

Lindahl

Wilson

1977

The Journal of Experimental Medicine

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336

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Using limiting dilutions of responding cells in mouse mixed leukocyte cultures, we obtained direct estimates of the minimum frequency of precursors of cytotoxic T lymphocytes (CTL.P) for a variety of antigens. Depending on the strain combination, there were as many as 4-15 CTL.P reactive to DBA/2 among 10(4) lymph node cells. Taking into account that only 5-10% of peripheral T lymphocytes have the potential to develop into cytotoxic T lymphocytes (CTLs) (6), this implies that at least 1-2% of all CTL.P are responsive to any given H-2 haplotype difference. Precursors of cytotoxic cells thus have the same high frequency of cells reactive to alloantigens of the major histocompatibility complex as found among proliferating cells in graft-vs.-host reactions and mixed lymphocyte interactions. The frequencies of CTL.P reactive to xenoantigens (rat) or trinitrophenyl-modified self were less than half the frequency of alloreactive CTL.P. A minority of the CTL.P specific for one H-2 haplotype were also reactive to a third party H-2 haplotype, presumably on the basis of recognition of shared determinants. By dilution of sensitized cells from single microcultures, it was shown that a single CTL.P undergoes a minimum of three to four cell divisions and generates at least 8-16 CTLs after antigenic activation.

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Histocompatibility antigen-activated cytotoxic T lymphocytes. I. Estimates of the absolute frequency of killer cells generated in vitro.

Cited by 88 publications

References 9 publications

Requirement for Both H-2Db and H-2Kd for the Induction of Diabetes by the Promiscuous CD8+ T Cell Clonotype AI4

Requirement for Both H-2Db and H-2Kd for the Induction of Diabetes by the Promiscuous CD8+ T Cell Clonotype AI4

Investigation of Peptide Involvement in T Cell Allorecognition Using Recombinant HLA Class I Multimers

Histocompatibility antigen-activated cytotoxic T lymphocytes. II. Estimates of the frequency and specificity of precursors.

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