Epitopic analysis of HLA DR molecule expression on alloreactive T-cell clones

We have studied the control and significance of IL-1 production in human leukocyte cultures during accessory cell-dependent, T lymphocyte mitogenesis using sensitive bioassays and immunolabeling techniques. In primary antigen-dependent systems like the MLR, IL-1 production was not detected in accessory cells (monocytes, dendritic cells) or T cells, suggesting that it is not an early product in these responses. However, monocytes could be induced to make IL-1 after interacting with sensitized antigen-specific T cells. Both alloreactive T cell clones or freshly prepared lymphoblasts induced IL-1 provided the monocytes carried the HLA-DR antigens to which the T cells were initially sensitized. Even in these circumstances, dendritic cells and B cells failed to make IL-1. The mechanism whereby activated T cells induce IL-1 in monocytes was explored. Supernatants from cocultures of monocytes and T cells or several recombinant cytokines induced little or no IL-1. A more potent antigen independent pathway of IL-1 induction was identified. IL-1 could be induced in third-party HLA-DR nonspecific monocytes in cocultures of alloreactive T cell clones or blasts and HLA-DR-specific dendritic cells. The induction was factor independent since dendritic cells and T blasts placed in a chamber separate from third-party monocytes by a semipermeable membrane did not induce monocyte IL-1. These results suggest that a cell contact mechanism rather than an IL-1-inducing factor leads to IL-1 production. The role of IL-1 in T cell proliferation was tested with a polyclonal anti-IL-1 antibody. The antibody failed to block the proliferation of primary T cells, or alloreactive T cell clones and blasts stimulated with HLA-specific monocytes or dendritic cells, even though IL-1 in the medium was neutralized.

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Alloreactive T-cell clones recognized DR-2-associated DQ morphism defined by DQα abd DQβ rflp. Adriana Zeevi, Loretta Di Vecchia, Sharon Rosenshine, Isabella Cascino, Masio Trucco, and Rene Duquesnoy; Department of Pathology, University of Pittsburgh, and Central Blood Bank, Pittsburgh, PA

Human Immunology ◽

10.1016/0198-8859(86)90232-6 ◽

1986 ◽

Vol 17 (2) ◽

pp. 189-190

Keyword(s):

T Cell ◽

Blood Bank ◽

T Cell Clones ◽

University Of Pittsburgh ◽

Cell Clones ◽

Alloreactive T Cell

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Th0 to Th1 switch of CD4 T cell clones specific from the 16-kDa antigen of Mycobacterium tuberculosis after successful therapy: lack of involvement of epitope repertoire and HLA-DR

Immunology Letters ◽

10.1016/j.imlet.2004.11.021 ◽

2005 ◽

Vol 98 (2) ◽

pp. 253-258 ◽

Cited By ~ 5

Author(s):

Nadia Caccamo ◽

Serena Meraviglia ◽

Francesco Dieli ◽

Amelia Romano ◽

Lucina Titone ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

T Cell ◽

Cd4 T Cell ◽

Successful Therapy ◽

T Cell Clones ◽

Hla Dr ◽

Cell Clones

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Alloreactive T-cell clones. Ly phenotypes predict both function and specificity for major histocompatibility complex products

Immunogenetics ◽

10.1007/bf00364755 ◽

1983 ◽

Vol 17 (2) ◽

pp. 147-165 ◽

Cited By ~ 13

Author(s):

Anjana Rao ◽

W. Jeffrey Allard ◽

Patrick G. Hogan ◽

Rene S. Rosenson ◽

Harvey Cantor

Keyword(s):

Major Histocompatibility Complex ◽

T Cell ◽

Major Histocompatibility ◽

T Cell Clones ◽

Complex Products ◽

Histocompatibility Complex ◽

Cell Clones ◽

Alloreactive T Cell

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Cell-type-specific cytotoxicity of anti-CD4 and anti-CD8 ricin immunotoxins against human alloreactive T-cell clones

Blood ◽

10.1182/blood.v74.7.2445.2445 ◽

1989 ◽

Vol 74 (7) ◽

pp. 2445-2454 ◽

Cited By ~ 5

Author(s):

FM Uckun ◽

DE Myers ◽

JA Ledbetter ◽

SL Wee ◽

DA Vallera

Keyword(s):

T Cell ◽

Cell Subset ◽

Target Cells ◽

Cell Type ◽

T Cell Clones ◽

First Order ◽

Cell Clones ◽

T Cell Clone ◽

Cell Type Specific ◽

Alloreactive T Cell

Abstract Potent T-cell subset-directed immunotoxins (ITs) were generated by conjugating the anti-CD4 monoclonal antibody (MoAb) G17–2 and the anti- CD8 MoAb G10.1 to the ribosome-inhibitory protein, ricin. The cell-type- specific cytotoxicities of the generated ITs were evaluated at the clonal level using human alloreactive T-cell clones. The kinetics of anti-CD4 ricin-induced inactivation of protein synthesis in target CD4+ cloned T-cells was first order with no detectable lag period and a maximum rate of 0.07 logs per hour (t10 = 13.6 hours; first-order rate constant/K = 0.17 hr-1). The alloantigen specific lytic function of the CD4+ cytolytic T-cell clone JMAC28 was acutely sensitive to anti-CD4 ricin, and no residual lytic activity against allogeneic targets was detectable 24 hours after treatment with as little as 0.5 mmol/L anti- CD4 ricin. Notably, both anti-CD4 ricin and anti-CD8 ricin elicited a selective and dose-dependent inhibition of clonal proliferation of target T-cell clones with a maximum kill of greater than 3 logs at 5 nmol/L. No significant “bystander effects” were observed for non-target cells. Bone marrow progenitor cells CFU-GM, BFU-E, and CFU-GEMM were only minimally affected by either IT. We conclude that these ITs show considerable potential for effective depletion of T-cell subpopulations from allogeneic donor marrow grafts for clinical graft-versus-host disease (GVHD) prophylaxis.

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Human alloreactive T cell clones for PLT

Human Immunology ◽

10.1016/0198-8859(80)90046-4 ◽

1980 ◽

Vol 1 (3) ◽

pp. 263

Author(s):

H. Inouye ◽

X. Chardonnens ◽

F.H. Bach

Keyword(s):

T Cell ◽

T Cell Clones ◽

Cell Clones ◽

Alloreactive T Cell

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Functional polymorphism of each of the two HLA-DR beta chain loci demonstrated with antigen-specific DR3- and DRw52-restricted T cell clones.

Journal of Experimental Medicine ◽

10.1084/jem.167.3.853 ◽

1988 ◽

Vol 167 (3) ◽

pp. 853-872 ◽

Cited By ~ 22

Author(s):

C Irlé ◽

D Jaques ◽

J M Tiercy ◽

S V Fuggle ◽

J Gorski ◽

...

Keyword(s):

T Cell ◽

Dna Sequencing ◽

Striking Difference ◽

Functional Polymorphism ◽

Beta Chain ◽

T Cell Clones ◽

Hla Dr ◽

Cell Clones ◽

Oligonucleotide Hybridization ◽

Hla Dr3

HLA-DR3- and HLA-DRw52-associated functional polymorphism was investigated with selected tetanus toxoid (TT)-specific T cell clones. We have shown earlier that HLA-DR antigens are encoded by two distinct loci, DR beta I and DR beta III. The alloantigenic determinant(s) defined by the serological HLA-DR3 specificity map to the former, while the supratypic HLA-DRw52 determinants map to DR beta III. Furthermore, we have recently recognized by DNA sequencing three alleles of HLA-DRw52 at locus DR beta III, referred to as 52 a, b, and c. Our objective was to correlate the pattern of T cell restriction with the gene products of individual DR beta chain loci and with the three newly described alleles of locus DR beta III. Among the selected T cell clones, 5 reacted exclusively when TT was presented by HLA-DR3+ APCs (TT-DR3-APC). In contrast, two T cell clones were stimulated by TT-DRw52-APC. More specifically, these two T cell clones (Clones 10 and 16) were stimulated by different subsets of TT-DRw52-APC. Clone 16 responded to some DR3 and TT-DRw6-APC, while clone 10 was stimulated by other TT-DR3 and TT-DRw6, and all TT-DR5-APC. This same pattern of DRw52 restriction was found in panel, as well as in family studies. Because this suggested a correlation with the pattern of DRw52 polymorphism observed earlier by DNA sequencing and oligonucleotide hybridization, the APC used in these experiments were typed for the 52 a, b, and c alleles of locus DR beta III by allele-specific oligonucleotide probes. This distribution overlapped exactly with the stimulation pattern defined by the T cell clones. Clone 16 responded to TT-52a-APC, clone 10 to TT-52b-APC, and both clones to a TT-52c-APC. The response of the T cell clones was inhibited differentially by mAbs to DR. Raising TT concentration, or increasing HLA-class II expression with INF-gamma both affected the magnitude of response of the TT-specific clones but did not modify their specificities. These results demonstrate that a restriction specificity can be attributed to the DR beta III locus and illustrate the functional relevance of the polymorphism observed at this locus. This is of special interest in view of the striking difference in the pattern of structural diversity among alleles of DR beta I and DR beta III.

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