Specific T Cell Responses against Minor Histocompatibility Antigens Cannot Generally Be Explained by Absence of Their Allelic Counterparts on the Cell Surface

PROTEOMICS ◽  
2018 ◽  
Vol 18 (12) ◽  
pp. 1700250 ◽  
Author(s):  
Helena M. Bijen ◽  
Chopie Hassan ◽  
Michel G. D. Kester ◽  
George M. C. Janssen ◽  
Pleun Hombrink ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Surface ◽  
T Cell Responses ◽  
Histocompatibility Antigens ◽  
Minor Histocompatibility Antigens ◽  
Cell Responses

IL-10 alters DC function via modulation of cell surface molecules resulting in impaired T-cell responses

2002 ◽  
Vol 215 (2) ◽  
pp. 162-172 ◽  
Author(s):  
Jacqueline M McBride ◽  
Thomas Jung ◽  
Jan E de Vries ◽  
Gregorio Aversa
Keyword(s):  
T Cell ◽  
Cell Surface ◽  
T Cell Responses ◽  
Cell Surface Molecules ◽  
Cell Responses ◽  
Surface Molecules ◽  
Dc Function

scholarly journals Specific interaction of lymphocyte function-associated antigen 3 with CD2 can inhibit T cell responses.

1993 ◽  
Vol 178 (1) ◽  
pp. 211-222 ◽  
Author(s):  
G T Miller ◽  
P S Hochman ◽  
W Meier ◽  
R Tizard ◽  
S A Bixler ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Surface ◽  
T Cell Activation ◽  
Cell Activation ◽  
Hepatitis B Surface Antigen ◽  
Specific Interaction ◽  
T Cell Responses ◽  
Accessory Cell ◽  
Lymphocyte Function ◽  
Cell Responses

Accessory cell surface molecules, such as T cell antigen CD2 and its ligand lymphocyte function-associated antigen 3 (LFA-3; CD58), are critical costimulatory pathways for optimal T cell activation in response to antigens. Interaction of CD2 with cell surface LFA-3 not only increases T cell/accessory cell adhesion, but also induces signal transduction events involved in the regulation of T cell responses. In this report, we show that specific interactions of LFA-3 with CD2 can result in T cell unresponsiveness to antigenic or mitogenic stimuli in vitro. By deletion of certain regions of the extracellular domain of LFA-3, we localized the CD2 binding site to the first domain of LFA-3. We then demonstrated that a soluble, purified first domain-LFA-3/IgG1 fusion protein (LFA3TIP) interacts with CD2 and binds to the same CD2 epitope as purified multimeric or cell surface-expressed LFA-3. LFA3TIP inhibits tetanus toxoid, hepatitis B surface antigen, anti-CD3 mAb, Con A, and phytohemagglutinin P-induced T cell proliferation, as well as xenogeneic and allogeneic mixed lymphocyte reactions (MLR). Unlike anti-LFA-3 or anti-CD2 monoclonal antibodies (mAbs) which inhibit T cell responses by blocking LFA-3/CD2 binding, LFA3TIP is capable of rendering T cells unresponsive to antigenic stimuli in situations where T cell activation is independent of CD2/LFA-3 interactions. Furthermore, LFA3TIP, but not blocking anti-CD2 mAbs, is capable of inducing T cell unresponsiveness to secondary stimulation in allogeneic MLR. This inhibition of T cell responses by LFA3TIP occurs through a different mechanism from that of mAbs to LFA-3 or CD2.

CD80-Transfected Acute Myeloid Leukemia Cells Induce Primary Allogeneic T-Cell Responses Directed at Patient Specific Minor Histocompatibility Antigens and Leukemia-Associated Antigens

Blood ◽  
1998 ◽  
Vol 92 (5) ◽  
pp. 1677-1684 ◽  
Author(s):  
Tuna Mutis ◽  
Ellen Schrama ◽  
Cornelis J.M. Melief ◽  
Els Goulmy
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
Hla Class I ◽  
T Cell Response ◽  
Leukemic Cells ◽  
Patient Specific ◽  
Minor Histocompatibility Antigens ◽  
Cell Responses ◽  
Cell Clones

Abstract Despite sufficient levels of HLA class I and class II expression, acute myeloid leukemia (AML) cells usually fail to induce a significant T-cell response in vitro. Therefore, we investigated whether in vitro modifications could enhance the T-cell stimulatory properties of AML cells. AML cells were either cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-4 (IL-4), and tumor necrosis factor- (TNF-), or transfected with the CD80 (B7.1) gene and used as stimulator cells for primed and unprimed allogeneic T cells. Cytokine treatment increased HLA class I and II expression, but did not induce CD80 on AML cells. Cytokine-treated AML cells efficiently presented nominal and allo-antigens to primed T-cell clones, induced strong T-cell proliferation in HLA mismatched mixed lymphocyte reactions (MLR), but failed to induce primary T-cell responses from an HLA identical bone marrow donor in MLR. In contrast, CD80-transfected AML cells induced T-cell proliferation of HLA-identical bone marrow donor peripheral blood mononuclear cell (PBMC) in primary MLR, allowing the generation of leukemia reactive CD4+ T-cell lines and clones. The majority of the generated oligoclonal (25 of 35) T-cell cultures showed patient specific reactivity that did not discriminate between patient’s leukemic cells and Epstein-Barr virus (EBV)-transformed B cells (EBV-LCL). The remaining 10 oligoclonal T-cell cultures recognized only leukemic cells. One of these latter leukemia reactive oligoclonal T cells was cloned. The majority of the clones (25 of 29) reacted against both leukemic cells and patient’s EBV-LCL. A minority of the T-cell clones with the CD4 phenotype (four of 29) showed strong HLA-DP restricted reactivity against leukemic cells, but not against patient’s EBV-LCL or against HLA-matched nonleukemic cells, indicating that their target antigens are preferentially expressed by leukemic cells. In conclusion, our study shows that the in vitro allogeneic T-cell response induced by CD80-transfected AML cells is mainly directed against patient’s specific minor histocompatibility antigens, while antigens preferentially expressed by leukemic cells can also trigger T-cell responses. © 1998 by The American Society of Hematology.

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