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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to elucidate the role of HLA class II molecules in generation of self-nonself discrimination of human T cells, we have analyzed T cell functions in an HLA class II-negative severe combined immunodeficiency patient. Patient PBL expressed no HLA-DR, -DQ, and -DP antigens as judged by immunofluorescence using mAb, and failed to elicit MLR responses from unrelated controls. Patient PBL contained mature T cells (CD3+ TCR alpha beta+) of the CD4 and CD8 subset, showing an apparently normal TCR diversity, as judged by use of anti-V beta 5, -V beta 6, -V beta 8, -V beta 12, and -V alpha 2 mAb. Patient PBL proliferated in response to anti-TCR/CD3 mAb and PHA, but not against recall Ag, despite immunization, and mounted proliferative, but not cytotoxic, responses against allogeneic cells. To find out whether the MLR responses were a consequence of self-nonself discrimination, the patient HLA-DR and -DQ genotype was determined using sequence specific oligonucleotide probes, revealing DRB1*0401 DQB1*0301 alleles, and MLR were set up against a panel of HLA-DR4 DQw3 stimulators matched or mismatched for DRB1*0401 DQB1*0301. Results showed no MLR against DRB1*0401 DQB1*0301 stimulators, but significant responses against stimulators expressing DRB1*0408 and/or DQB1*0302 alleles. Moreover, the DRB1*0401 DQB1*0301 APC reconstituted proliferation of patient PBL against PPD; this response was completely blocked by an anti-IL-2R (p55) mAb and partially also by anti-HLA-DR and -DQ mAb, indicating recognition of these molecules as restriction element presenting Ag--i.e., as self--by patient T cells. In conclusion, the novel demonstration of self-nonself discrimination by T cells from an HLA class II-negative SCID patient suggests that it may not be absolutely dependent on regular HLA class II expression within the differentiation environment in humans.
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PMID:Allorecognition and T cell repertoire selection in severe combined immunodeficiency lacking HLA class II antigens. 153 39

The cellular distribution of two anti-HLA-DR-like monoclonal antibodies was examined. The reagents showed typical affinity to E- cells, adherent cells and activated T cells. Functionally, they affected the presentation of PPD antigen from APC to T cells in autologous and allogeneic mixed lymphocyte reaction. One of them significantly influenced the proliferation of T helper cells activated polyclonally with PHA.
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PMID:Examination of two anti-HLA-DR-like monoclonal antibodies. 242 3

Antigen-specific Ts against DTH to BCG were induced in vitro by culturing the splenic T cells of C3H/He mice together with the lined macrophage, SL-1, pulsed with PPD. The suppressor activity was determined by the suppression of DTH in CY-treated syngeneic recipients which had received the cultured cells before BCG sensitization. SL-1 cells express I-A and I-J antigens on the surface, while SL-4 cells, which originated in the same mouse strain as SL-1, do not express any Ia antigens. When I-A antigens on SL-1 were blocked by anti-I-A antibody without complement before PPD-pulsing, the induction of Ts was rather enhanced. When I-J antigens on SL-1 were blocked by anti-I-J alloantiserum, no Ts were induced. Instead, these I-J-blocked and PPD-pulsed SL-1 cells induced effector cells of DTH in vitro. Ia-negative lined macrophage SL-4 cells did not show any activity either in suppressor or in effector cell induction. From these results, we propose a model for the immune modulation led by APC.
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PMID:Accessory cell function of a lined macrophage in the induction of suppressor T cells in vitro. 294 5

Murine monoclonal antibodies (MoAb) to three distinct Ia-like molecules were studied for their inhibitory effects on antigen- and alloantigen-induced T cell proliferations. The MoAb were classified into three groups according to the molecules they recognized. Both the group I MoAb reacting with DR molecules and the group III MoAb were capable of inhibiting T cell proliferative responses to PPD- and HSV-Ag-pulsed APC, autologous B-LCL, and alloantigens. On th other hand, the group II MoAb, which reacted with a determinant on the molecule carrying MB1 determinants, was only capable of inhibiting T cell responses to alloantigens. These results suggest that the structure of the molecules correlates with the functional repertoire of the human Ia-like antigens.
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PMID:The role of three distinct Ia-like antigen molecules in human T cell proliferative responses: effect of monoclonal anti-Ia-like antibodies. 617 89

In this study, in vitro immune responses to PPD were analysed using T cell clones and monoclonal antibodies against DR and MB antigens. Effects of monoclonal antibodies on proliferative responses of PBM (peripheral blood mononuclear cell) to PPD (primary response) and on those of PPD-primed PBM to PPD (secondary response) were tested. The results showed that anti-DR monoclonal antibodies, HU-4 and HU-20, inhibited PPD specific PBM proliferative responses through inhibition of antigen presentation with steric hindrance to DR antigens of APC (antigen presenting cell). In contrast, an anti-MB 3 monoclonal antibody, HU-18, did not affect any of the responses tested. Furthermore, three PPD specific T cell clones established were restricted by DR molecules, but not by MB molecules. Thus, it was concluded that DR antigens played an important role in the immune responses to PPD. This result is different from the findings in mice where I-A antigens serve as restriction molecules in PPD specific responses. This difference in restriction molecules between species was discussed.
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PMID:[Analysis of in vitro immune responses in humans using T cell clones and monoclonal antibodies]. 620 87

To further delineate the functional defects of bm12 mice in antigen presentation, we analyzed antigen-specific T lymphocyte clones derived from B6 or bm12 for their ability to recognize antigens presented on either B6 or bm12 APC. Both complex antigens, such as PPD and GAT, and restricted antigens, such as beef insulin, were used. Our results indicate that for complex antigens, more than 50% of the B6 T lymphocyte clones recognized antigens only if presented by B6 APC, whereas the rest could not discriminate B6 from bm12 APC. Similarly, bm12 T lymphocyte clones responding to complex antigens could be divided into two groups depending on the sources of the APC. We have also isolated B6 T lymphocyte clones specific for the more restricted antigen, beef insulin, to which bm12 failed to respond. All B6 T lymphocyte clones could be stimulated only with B6 APC and not with bm12 APC. These data are consistent with the notion that there are antigen-specific association sites on the Ia molecule, and that complex antigens have more than one such association site. Furthermore, these studies demonstrate that both the gain and loss determinants associated with the bm12 mutation are recognized by a significant number of bm12 and B6 antigen-specific T lymphocyte clones, respectively, thus defining the importance of this region of the A beta polypeptide chain in antigen presentation.
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PMID:Assessment of antigen-specific restriction sites on Ia molecules as defined by the bm12 mutation. 620 61

Single-cell resolution cytokine ELISPOT assays are increasingly used to gain insights into clonal sizes of type 1 and type 2 effector T cell populations in vivo. However, ELISPOT assays permitting monitoring of regulatory IL-10-producing T cells have so far not been established. Unlike IFN-gamma, IL-2, IL-4, and IL-5 assays performed on PBMC in which the recall antigen-induced cytokine spots are T cell-derived, we show here that in such assays IL-10 is primarily monocyte-derived. T cell-derived IL-10 spots were 80 x 10(3) microm(2) in size, seven times larger than spots produced by monocytes, and B cells produced even smaller spots. Based on spot size gating and the use of B cells as APC, we have established test conditions that permit measurement of cognate IL-10 production by low-frequency antigen-specific T cells. IL-10-producing PPD-specific CD4(+) T cells were detected in frequencies comparable to IFN-gamma-secreting CD4(+) T cells in tuberculosis patients, but not in uninfected healthy control individuals. In contrast, IL-10-secreting CD4(+) T cells specific for a panel of recall antigens could not be detected in frequencies >1/100,000 in healthy individuals whose CD4(+) cells responded to these antigens with type 1 or type 2 cytokine production in the 1:100,000-1:1000 frequency range. Therefore, the induction of IL-10-producing T cells seems to be under tighter control than that of Th1/Th2 cells, apparently confined to states of chronic immune stimulation. Access to low-frequency immune monitoring of IL-10-producing T cells will provide new insights into the role of regulatory T cells in health and disease.
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PMID:Detection of low-frequency antigen-specific IL-10-producing CD4(+) T cells via ELISPOT in PBMC: cognate vs. nonspecific production of the cytokine. 1296 52