Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 5 de 5
Filter
Add more filters










Database
Language
Publication year range
1.
Virology ; 363(1): 113-23, 2007 Jun 20.
Article in English | MEDLINE | ID: mdl-17320138

ABSTRACT

Virus-specific CD4(+) T cells contribute to effective virus control through a multiplicity of mechanisms including direct effector functions as well as "help" for B cell and CD8(+) T cell responses. Here, we have used the lymphocytic choriomeningitis virus (LCMV) system to assess the minimal constraints of a dominant antiviral CD4(+) T cell response. We report that the core epitope derived from the LCMV glycoprotein (GP) is 11 amino acids in length and provides optimal recognition by epitope-specific CD4(+) T cells. Surprisingly, this epitope is also recognized by LCMV-specific CD8(+) T cells and thus constitutes a unique viral determinant with dual MHC class I- and II-restriction.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , Epitopes, T-Lymphocyte/immunology , Histocompatibility Antigens Class II/immunology , Histocompatibility Antigens Class I/immunology , Immunodominant Epitopes/immunology , Amino Acid Sequence , Animals , Epitope Mapping , Epitopes, T-Lymphocyte/chemistry , Lymphocytic choriomeningitis virus/immunology , Mice , Molecular Sequence Data , Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell/immunology , Receptors, Antigen, T-Cell/metabolism , T-Lymphocytes, Cytotoxic/immunology
2.
Autoimmunity ; 37(8): 555-67, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15763918

ABSTRACT

We previously described the generation of non-obese diabetic (NOD) mice expressing a transgenic T cell receptor (TCR) specific for peptide epitope 286-300 of the diabetes related self antigen, glutamic acid decarboxylase (GAD)65 in the context of I-A(g7) class II MHC, that are paradoxically protected from diabetes. In this report, we examine the atypical CD8+ cells in these mice. Unlike typical class II restricted TCR transgenic mice, GAD286 mice have normal numbers of CD8+ cells, half of which express high levels of the transgenic TCR. These MHC mismatched CD8+ cells persist in the periphery and proliferate to GAD286-300 peptide in vitro and in vivo in a class II restricted fashion. Interestingly, the CD8+ tetramer(-) T cells that are expressing endogenous TCR can delay diabetes induction in a transfer model, as we previously showed for CD4+ tetramer+ T cells in these mice. The MHC mismatched CD8+ cells appear to be positively selected in an atypical fashion, in that they do not upregulate CD69 or reexpress CD44, and they escape negative selection. We find that production of these CD8+ cells is not dependent on NOD thymus or high affinity of the TCR, but is dependent on the atypical TCR transgenic thymic environment.


Subject(s)
Autoantigens/immunology , CD8-Positive T-Lymphocytes/immunology , Diabetes Mellitus, Type 1/immunology , Epitopes, T-Lymphocyte/immunology , Histocompatibility Antigens Class II/immunology , Receptors, Antigen, T-Cell/immunology , Animals , Autoantigens/genetics , Clonal Deletion/immunology , Diabetes Mellitus, Type 1/genetics , Epitopes, T-Lymphocyte/genetics , Glutamate Decarboxylase/genetics , Glutamate Decarboxylase/immunology , Mice , Mice, Inbred NOD , Mice, Transgenic , Receptors, Antigen, T-Cell/genetics
3.
J Clin Invest ; 112(6): 902-14, 2003 Sep.
Article in English | MEDLINE | ID: mdl-12975475

ABSTRACT

To detect and characterize autoreactive T cells in diabetes-prone NOD mice, we have developed a multimeric MHC reagent with high affinity for the BDC-2.5 T cell receptor, which is reactive against a pancreatic autoantigen. A distinct population of T cells is detected in NOD mice that recognizes the same MHC/peptide target. These T cells are positively selected in the thymus at a surprisingly high frequency and exported to the periphery. They are activated specifically in the pancreatic LNs, demonstrating an autoimmune specificity that recapitulates that of the BDC-2.5 cell. These phenomena are also observed in mouse lines that share with NOD the H-2g7 MHC haplotype but carry diabetes-resistance background genes. Thus, a susceptible haplotype at the MHC seems to be the only element required for the selection and emergence of autoreactive T cells, without requiring other diabetogenic loci from the NOD genome.


Subject(s)
Alleles , Autoimmunity , CD4-Positive T-Lymphocytes/immunology , Diabetes Mellitus, Type 1/immunology , Major Histocompatibility Complex/genetics , Animals , Autoantigens/immunology , CD4-Positive T-Lymphocytes/physiology , Diabetes Mellitus, Type 1/metabolism , Female , Haplotypes , Hybridomas/cytology , Hybridomas/immunology , Hybridomas/metabolism , Mice , Mice, Inbred NOD , Mice, Transgenic , Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell/metabolism , Thymus Gland/cytology , Thymus Gland/metabolism
4.
J Immunol ; 170(1): 123-31, 2003 Jan 01.
Article in English | MEDLINE | ID: mdl-12496391

ABSTRACT

Subtle differences oppose CD4+ to CD8+ T cell physiologies that lead to different arrays of effector functions. Interestingly, this dichotomy has also unexpected practical consequences such as the inefficacy of many MHC class II tetramers in detecting specific CD4+ T cells. As a mean to study the CD4+ anti-OVA response in H-2(d) and H-2(b) genetic backgrounds, we developed I-A(d)- and I-A(b)-OVA recombinant MHC monomers and tetramers. We were able to show that in this particular system, despite normal biological activity, MHC class II tetramers failed to stain specific T cells. This failure was shown to be associated with a lack of cooperation between binding sites within the tetramer as measured by surface plasmon resonance. This limited cooperativeness translated into a low "functional avidity" and very transient binding of the tetramers to T cells. To overcome this biophysical barrier, recombinant artificial APC that display MHC molecules in a lipid bilayer were developed. The plasticity and size of the MHC-bearing fluorescent liposomes allowed binding to Ag-specific T cells and the detection of low numbers of anti-OVA T cells following immunization. The same liposomes were able, at 37 degrees C, to induce the full reorganization of the T cell signaling molecules and the formation of an immunological synapse. Artificial APC will allow T cell detection and the dissection of the molecular events of T cell activation and will help us understand the fundamental differences between CD4+ and CD8+ T cells.


Subject(s)
Antigen-Presenting Cells/metabolism , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Cell Communication/genetics , Cell Communication/immunology , DNA, Recombinant/immunology , Ovalbumin/genetics , Ovalbumin/immunology , Peptide Fragments/genetics , Peptide Fragments/immunology , Animals , Antigen Presentation/genetics , Antigen-Presenting Cells/immunology , Cell Adhesion/immunology , Cell Aggregation/genetics , Cell Aggregation/immunology , Chickens , Epitopes, T-Lymphocyte/analysis , Histocompatibility Antigens Class II/genetics , Histocompatibility Antigens Class II/immunology , Histocompatibility Antigens Class II/metabolism , Humans , Hybridomas/chemistry , Interphase/immunology , Liposomes/analysis , Lymphocyte Activation/genetics , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Transgenic , Ovalbumin/metabolism , Peptide Fragments/metabolism , Solubility , Staining and Labeling , Surface Plasmon Resonance , T-Lymphocyte Subsets/chemistry , T-Lymphocyte Subsets/immunology
5.
Immunity ; 17(2): 191-200, 2002 Aug.
Article in English | MEDLINE | ID: mdl-12196290

ABSTRACT

CD4 T cells are pivotal for effective immunity, yet their initial differentiation into effector subsets after infection remains poorly defined. We examined CD4 T cells specific for the immunodominant Leishmania major LACK antigen using MHC/peptide tetramers and IL-4 reporter mice. Comprising approximately 15 cells/lymph node in naive mice, LACK-specific T cells expanded over 100-fold, and 70% acquired IL-4 expression by 96 hr. Despite their pathogenic role in susceptible mice, LACK-specific precursor frequency, expansion, and IL-4 expression were comparable between susceptible and resistant mice. When injected with unrelated antigen, Leishmania efficiently activated IL-4 expression from naive antigen-specific T cells. CD4 subset polarization in this highly characterized model occurs independently from IL-4 expression by naive T cells, which is activated indiscriminately after parasitism.


Subject(s)
Antigens, Protozoan/immunology , Interleukin-4/genetics , Leishmania major/immunology , Leishmaniasis, Cutaneous/immunology , Protozoan Proteins/immunology , T-Lymphocytes, Helper-Inducer/immunology , Animals , CD4-Positive T-Lymphocytes/immunology , Female , Gene Expression , Hematopoietic Stem Cells/immunology , Histocompatibility Antigens Class II/immunology , Immunodominant Epitopes/immunology , Immunophenotyping , Male , Mice , Mice, Inbred BALB C , T-Lymphocytes, Helper-Inducer/cytology , Time Factors
SELECTION OF CITATIONS
SEARCH DETAIL
...