scholarly journals High Levels of a Major Histocompatibility Complex II–Self Peptide Complex on Dendritic Cells from the T Cell Areas of Lymph Nodes

1997 ◽  
Vol 186 (5) ◽  
pp. 665-672 ◽  
Author(s):  
Kayo Inaba ◽  
Maggie Pack ◽  
Muneo Inaba ◽  
Hiraki Sakuta ◽  
Frank Isdell ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Mhc I ◽  
Peptide Complex ◽  
Mhc Ii ◽  
Histocompatibility Complex ◽  
Peripheral Lymph ◽  
Free Media ◽  
Very High

T lymphocytes recirculate continually through the T cell areas of peripheral lymph nodes. During each passage, the T cells survey the surface of large dendritic cells (DCs), also known as interdigitating cells. However, these DCs have been difficult to release from the lymph node. By emphasizing the use of calcium-free media, as shown by Vremec et al. (Vremec, D., M. Zorbas, R. Scollay, D.J. Saunders, C.F. Ardavin, L. Wu, and K. Shortman. 1992. J. Exp. Med. 176:47–58.), we have been able to release and enrich DCs from the T cell areas. The DCs express the CD11c leukocyte integrin, the DEC-205 multilectin receptor for antigen presentation, the intracellular granule antigens which are recognized by monoclonal antibodies M342, 2A1, and MIDC-8, very high levels of MHC I and MHC II, and abundant accessory molecules such as CD40, CD54, and CD86. When examined with the Y-Ae monoclonal which recognizes complexes formed between I-Ab and a peptide derived from I-Eα, the T cell area DCs expressed the highest levels. The enriched DCs also stimulated a T-T hybridoma specific for this MHC II–peptide complex, and the hybridoma underwent apoptosis. Therefore DCs within the T cell areas can be isolated. Because they present very high levels of self peptides, these DCs should be considered in the regulation of self reactivity in the periphery.

scholarly journals P04.06 mucosal immunization with a cDC1-targeted CTA1 adjuvant vaccine confers protection against melanoma metastasis

2020 ◽  
Vol 8 (Suppl 2) ◽  
pp. A39.1-A39
Author(s):  
M Arabpour ◽  
S Paul ◽  
R Kiffin ◽  
HG Wiktorin ◽  
K Hellstrand ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Immune Responses ◽  
Pulmonary Metastases ◽  
T Cell Immunity ◽  
Metastasis Formation ◽  
Mhc I ◽  
Mhc Ii ◽  
Cell Immunity

BackgroundSpecific targeting of anti-cancer vaccines to dendritic cells (DCs) has been shown to mount efficient immune responses against tumor cells. Classical CD103+dendritic cells (also called cDC1) have an inherent ability to cross-present antigens to CD8+ cytotoxic T cells. Here we have explored an anti-tumor vaccine that specifically targets cDC1 cells for protection against and elimination of metastatic melanoma. The vaccine contains the cholera toxin A1 subunit (CTA1) adjuvant and is targeted to cDC1 cells through an anti-CD103 single chain antibody (CD103 scFv).Material and MethodsC57BL/6 mice were injected with wild type or ovalbumin (OVA) expressing B16 melanoma cells either subcutaneously (s.c.) to establish solid tumors, or intravenously (i.v.) to allow the formation of pulmonary metastases. Before or after establishment of tumors, mice were intra-nasally inoculated with a vaccine composed of a CD103 scFv element fused to the adjuvant CTA1 and the MHC I H2kd-restricted OVA epitope SIINFEKL together with the MHC II H2kd-restricted OVA epitope p323 or just the p323 peptide alone (i.e. CTA1-SIINFEKL-p323-CD103 and CTA1-p323-CD103, respectively). Control mice were inoculated with PBS. The growth of solid tumors was carefully monitored and the development of pulmonary metastases was determined 2–3 weeks after tumor cell injection. In addition, antigen-specific T cell immunity following intranasal immunization was evaluated.ResultsTargeting MHC I and MHC II tumor cell epitopes to cDC1, via CD103 ScFv, in conjunction with the CTA1 adjuvant elicited strong tumor specific and protective CD8+ T cell responses as well as CD4+ T cell immunity. Immunization with the CTA1-SIINFEKL-p323-CD103 vaccine significantly reduced the growth of established solid B16F1-OVA melanomas (P<0.001) and potently prevented metastasis formation (P<0.01). Control immunizations with the CTA1-p323-CD103 vaccine tended to reduce metastasis, but tumor-specific CD8+ T cells were required for full therapeutic protection.ConclusionTargeting tumor specific CD8+ T cell epitopes to cDC1, in the context of a powerful adjuvant such as CTA1, leads to the development of efficient anti-tumor immune responses. Our results point towards the utility of cDC1-targeted vaccines in the treatment of established tumors or as a means to prevent metastasis formation.Disclosure InformationM. Arabpour: None. S. Paul: None. R. Kiffin: None. H.G. Wiktorin: None. K. Hellstrand: None. N. Lycke: None. A. Martner: None.

scholarly journals Self major histocompatibility complex class I antigens expressed solely in lymphoid cells do not induce tolerance in the CD4+ T cell compartment.

1996 ◽  
Vol 184 (4) ◽  
pp. 1573-1578 ◽  
Author(s):  
R Schulz ◽  
A L Mellor
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Lymphoid Cells ◽  
Cd4 T Cell ◽  
Cell Compartment ◽  
Mhc I ◽  
Mhc Ii ◽  
Histocompatibility Complex ◽  
Self Peptides

Transgenic mice expressing self major histocompatibility complex (MHC) class I (H-2Kb) antigen solely in lymphoid cell lineages do not acquire tolerance to H-2Kb expressed on skin grafts. H-2Kb-specific cytotoxic T cell responses were completely abrogated in these mice, even after they had rejected skin grafts. Moreover, thymocytes expressing T cell receptors that confer H-2Kb reactivity on cytotoxic CD8+ T cells were eliminated. The ability to reject grafts correlated with the presence of a novel population of H-2Kb-reactive CD4+ T cells. At least some of these CD4+ T cells recognize peptides derived from H-2Kb by processing. We conclude that self MHC I antigens induce tolerance in the CD8 T cell compartment via negative selection when expressed exclusively by lymphoid cells. In contrast, tolerance to MHC class II-restricted self peptides derived by processing of such MHC I antigens is not induced in the CD4 T cell compartment. This suggests that effective transfer of self antigens from lymphoid cells to MHC II-positive cells that can process and present them as self peptides to thymocytes or CD4+ T cells does not take place in vivo. Thus, sequestration of self antigens and MHC II molecules in distinct cell types in the thymic microenvironment allows potentially autoreactive and functionally competent CD4+ T cells that recognize cryptic MHC II-restricted self peptides to mature into the peripheral T cell repertoire under normal physiological circumstances.

scholarly journals Cd11c+B220+Gr-1+ Cells in Mouse Lymph Nodes and Spleen Display Characteristics of Plasmacytoid Dendritic Cells

2001 ◽  
Vol 194 (8) ◽  
pp. 1171-1178 ◽  
Author(s):  
Hideki Nakano ◽  
Manabu Yanagita ◽  
Michael Dee Gunn
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Plasmacytoid Dendritic Cells ◽  
High Endothelial Venules ◽  
Histocompatibility Complex ◽  
Specific Variation ◽  
Low Levels ◽  
And Control ◽  
Deficient Mice

Human plasmacytoid dendritic cells (pDCs) are major producers of IFNα, are activated by CpG motifs, and are believed to enter lymph nodes (LNs) via L-selectin dependent extravasation across high endothelial venules. To identify a similar murine DC type, CD11c+ cells in the LNs of L-selectin–deficient and control BALB/c mice were compared, revealing a population of CD11c+CD11b− cells that is reduced 85% in the LNs of L-selectin–deficient mice. These cells are Gr-1+B220+CD19−, either CD4+ or CD8+, and localize within T cell zones of LNs. Freshly isolated CD11c+Gr-1+ cells express major histocompatibility complex class II at low levels, display a plasmacytoid morphology, and survive poorly in culture. Their survival is increased and they develop a DC-like morphology in interleukin 3 and CpG. Like human pDCs, CD11c+Gr-1+ cells stimulate T cell proliferation after activation with CpG and produce IFNα after stimulation with influenza virus. These cells also display a strain-specific variation in frequency, being fivefold increased in the LNs of BALB/c relative to C57BL/6 mice. These CD11c+CD11b−B220+Gr-1+ cells appear to be the murine equivalent of human pDCs.

scholarly journals The V beta complementarity determining region 1 of a major histocompatibility complex (MHC) class I-restricted T cell receptor is involved in the recognition of peptide/MHC I and superantigen/MHC II complex.

1994 ◽  
Vol 179 (4) ◽  
pp. 1087-1097 ◽  
Author(s):  
M Bellio ◽  
Y C Lone ◽  
O de la Calle-Martin ◽  
B Malissen ◽  
J P Abastado ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Mhc Class I ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Class I ◽  
Mhc I ◽  
Mhc Ii ◽  
Histocompatibility Complex ◽  
Complementarity Determining Region

We investigated the role of the complementarity determining region 1 (CDR1) of T cell receptor (TCR) beta chain both in antigen/major histocompatibility complex I (MHC I) and in superantigen (SAg)/MHC II complex recognition. Residues 26 to 31 of the V beta 10 domain of a TCR derived from an H-2Kd-restricted cytotoxic clone were individually changed to alanine, using site-directed mutagenesis, and the mutated TCR beta chains were transfected along with the wild-type TCR alpha chain into a TCR alpha-beta-T hydridoma. These mutations affected antigen/H-2Kd complex recognition, although to a different extent, as estimated by interleukin 2 production. Certain mutations also affected differently the recognition of two Staphylococcal toxins, exfoliative toxin and Staphylococcal enterotoxin C2, presented by HLA-DR1. Whereas mutation of residues D30 or T31 affect the recognition of both toxins, residues T26, L27, and H29 are critical for the recognition of only one of the SAgs. These observations demonstrate the participation of the CDR1 region in the recognition of peptide/MHC class I as well as SAg/MHC II complexes.

Blood dendritic cells in cattle infected with bovine leukemia virus (BLV): isolation and phenotyping

2012 ◽  
Vol 15 (4) ◽  
pp. 599-634
Author(s):  
M. Szczotka ◽  
J. Kuźmak ◽  
K. Kostro ◽  
D. Bednarek ◽  
M. Purzycka
Keyword(s):  
Flow Cytometry ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Mhc Class Ii ◽  
Leukemia Virus ◽  
Mhc I ◽  
Mhc Ii ◽  
Antigen Presenting ◽  
Very High

AbstractDendritic cells (DCs) are most potent antigen presenting cells (APCs) with unique ability to prime effective immune responses. They express higher levels of MHC class II and accesory molecules on their surface, than other professional APCs. The investigations were performed on DCs generated from blood with the use of microbeads magnetically labeled with mouse anti human CD14. Flow cytometry was applied for determination of DCs immunophenotype in healthy and naturally infected with BLV cattle. For immunophenotyping mouse monoclonal antibodies anti bovine: CD11a, CD11b, CD11c, MHC-I and MHC-II were used. Our results demonstrated that dendritic cells infected with BLV expressed very high percentage of determinants: CD11a, CD11b, CD11c, MHC-I and MHC-II class. Leukaemic DCs exhibited DCs morphology and had a phenotype of mature DCs. The expression of gp51 glycoprotein of BLV on leukaemic DCs was detected in flow cytometry investigations.

scholarly journals The Major Histocompatibility Complex Class II Alleles Mamu-DRB1*1003 and -DRB1*0306 Are Enriched in a Cohort of Simian Immunodeficiency Virus-Infected Rhesus Macaque Elite Controllers

2007 ◽  
Vol 82 (2) ◽  
pp. 859-870 ◽  
Author(s):  
Juan P. Giraldo-Vela ◽  
Richard Rudersdorf ◽  
Chungwon Chung ◽  
Ying Qi ◽  
Lyle T. Wallace ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Viral Replication ◽  
Rhesus Macaques ◽  
Complex Class ◽  
Elite Controllers ◽  
Mhc Ii ◽  
Histocompatibility Complex ◽  
Immunodeficiency Virus

ABSTRACT The role of CD4+ T cells in the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication is not well understood. Even though strong HIV- and SIV-specific CD4+ T-cell responses have been detected in individuals that control viral replication, major histocompatibility complex class II (MHC-II) molecules have not been definitively linked with slow disease progression. In a cohort of 196 SIVmac239-infected Indian rhesus macaques, a group of macaques controlled viral replication to less than 1,000 viral RNA copies/ml. These elite controllers (ECs) mounted a broad SIV-specific CD4+ T-cell response. Here, we describe five macaque MHC-II alleles (Mamu-DRB*w606, -DRB*w2104, -DRB1*0306, -DRB1*1003, and -DPB1*06) that restricted six SIV-specific CD4+ T-cell epitopes in ECs and report the first association between specific MHC-II alleles and elite control. Interestingly, the macaque MHC-II alleles, Mamu-DRB1*1003 and -DRB1*0306, were enriched in this EC group (P values of 0.02 and 0.05, respectively). Additionally, Mamu-B*17-positive SIV-infected rhesus macaques that also expressed these two MHC-II alleles had significantly lower viral loads than Mamu-B*17-positive animals that did not express Mamu-DRB1*1003 and -DRB1*0306 (P value of <0.0001). The study of MHC-II alleles in macaques that control viral replication could improve our understanding of the role of CD4+ T cells in suppressing HIV/SIV replication and further our understanding of HIV vaccine design.

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