HLA Class II-Restricted CD4+ T Cell Responses Directed Against Influenza Viral Antigens Postinfluenza Vaccination

Danke, Nancy A.; Kwok, William W.

doi:10.4049/jimmunol.171.6.3163

Cited by 92 publications

(97 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The tetanus peptide TT 947-966 was used as antigenic peptide for stimulation of T cells from DRB1*1101-positive donors, the peptide HA 307-319 for DRB1*0401 and DRB1*0101 donors. Both peptides have been predicted as ligands for the selected HLA-DR molecules by a prediction algorithm (www.syfpeithy.de) [26] and previous studies [21,27]. Affinity of the peptides to Hsp70 has been tested in a Europiumimmunofluorescence assay as described in Materials and methods.…”

Section: Resultsmentioning

confidence: 99%

“…MHC class II tetramers allow the visualization of antigen-specific T cells in peripheral blood at a frequency as low as 0.003% [21]. By combining tetramer and CSFE staining, we could estimate the number of activated T cell precursors.…”

Section: Discussionmentioning

confidence: 99%

“…Peptides representing MHC class II-restricted epitopes from tetanus toxoid (TT) and influenza hemagglutinin (HA) were used to stimulate human CD4 + T cells from pre-immunized donors in vitro; antigen specificity of proliferating cells was confirmed by fluorescent MHC class II tetramers [19][20][21][22]. Proliferation of antigen-specific CD4 + T cells was found to be enhanced by Hsp70:peptide complexes as compared to peptide alone.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The heat shock protein Hsp70 enhances antigen-specific proliferation of human CD4+ memory T cells

et al. 2005

View full text Add to dashboard Cite

Heat shock proteins (HSP) can interact with a wide variety of peptides and the resulting HSP:peptide complexes are known to be highly immunogenic. The ability of HSP:peptide complexes to elicit CD8 + T cell responses by cross-presentation of exogenous antigen via MHC class I is well known. In contrast, their role in the activation of CD4 + T cells is less clearly defined, although several recent studies in mice and T cell lines suggest an involvement of HSP in the presentation of antigenic peptides via MHC class II. In this study we have investigated the potential of antigenic peptides from tetanus toxin and influenza hemagglutinin complexed to the human stress-inducible Hsp70 to enhance activation and proliferation of human memory CD4 + T cells. Hsp70:peptide complexes were found to amplify the proliferation of antigen-specific CD4 + T cells as confirmed by HLA-DR tetramer staining. Complex formation of the antigenic peptide with Hsp70 was absolutely required to elicit an antigen-specific amplification. This effect was most pronounced at low doses of antigen and decreasing APC/CD4 + T cell ratios. Taken together, we show the potential of Hsp70 to enhance antigen-specific CD4 + T cell proliferation and to increase the immunogenicity of presented peptides in human CD4 + T cells.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The heat shock protein Hsp70 enhances antigen-specific proliferation of human CD4+ memory T cells

et al. 2005

View full text Add to dashboard Cite

show abstract

“…T cells targeting a non-persistent viral infectious agent, i.e. influenza A are in the range of 0.00012-0.0061% of CD4 + T cells and exhibit a 'memory phenotype' defined by the CD62L-CD28 + , CD45RA ) expression pattern [13,21,22]. In contrast, ex vivo visualization of MTB-reactive T cells can be achieved without the need for in vitro manipulation, frequencies may reach several per cent of the CD4 + T-cell population (see Figs.…”

Section: Discussionmentioning

confidence: 99%

MHC class II Tetramer Guided Detection of Mycobacterium tuberculosis‐specific CD4⁺ T Cells in Peripheral Blood from Patients with Pulmonary Tuberculosis

Höhn¹,

Kortsik²,

Zehbe³

et al. 2007

Scand J Immunol

View full text Add to dashboard Cite

Novel diagnostic tools are needed to diagnose latent infection and to provide biologically meaningful surrogate markers to define cellular immune responses against Mycobacterium tuberculosis (MTB). Interferon gamma‐based assays have recently been developed in addition to the more than 100‐year‐old tuberculin skin test (TST) for the immune diagnosis of MTB in blood. The advent of soluble MHC/peptide tetramer molecules allows to objectively enumerate antigen‐specific T cells. We identified novel MHC class II‐restricted MTB epitopes and used HLA‐DR4 tetrameric complexes to visualize ex vivo CD4+ T cells directed against the antigens Ag85B and the 19‐kDa lipoprotein, shared between MTB and other Mycobacterium species, and CD4+ T cells which recognize the MTB‐associated ESAT‐6 antigen. MTB‐reactive CD4+ T cells reside predominantly in the CD45RA+ CD28+ and CD45− CD28+ T‐cell subset and recognize naturally processed and presented MTB epitopes. HLA‐DR4‐restricted, Ag85B or ESAT‐6‐specific CD4+ T cells show similar dynamics over time in peripheral blood mononuclear cells (PBMC) when compared with CD8+ T cells directed against the corresponding HLA‐A2‐presented MTB epitopes in patients with pulmonary MTB infection and subsequent successful therapy. This was not found to be true for T‐cell responses directed against the 19‐kDa lipoprotein. The dissection of the cellular immune response in M. tuberculosis infection will enable novel strategies for monitoring MTB vaccine candidates and to gauge CD4+ T cells directed against MTB.

show abstract

“…100 While reliable protocols exist for the synthesis of pMHC class I multimers, pMHC class II multimers are more difficult to produce and are less promising for direct ex vivo detection of antigenspecific CD4 ϩ T cells, due to the low signal to background noise ratio obtained. However, for viral systems it has been reported that pMHC class II multimers can reveal Ag-specific CD4 ϩ T cells in nonpreselected PBMC, 101,102 and differentiate between CD4 ϩ Tcell clones with high and low TCR avidities. 103 While multimers reveal overall numbers of specific T cells, they can be combined with other assays in order to obtain insights into the phenotypic and functional properties of multimer-binding T cells.…”

Section: Immune Monitoringmentioning

confidence: 99%

Recent advances in tumour antigen‐specific therapy: In vivo veritas

Mahnke

Speiser

Luescher

et al. 2004

Intl Journal of Cancer

View full text Add to dashboard Cite

Modern cancer therapies should strive not only to eliminate malignant tissues but also to preserve healthy tissues and the patient's quality of life. Antigen-specific immunotherapy approaches are promising for either aspect since they are designed to only act against tissues expressing 1 or more specified tumour antigens. In order to develop successful vaccine and adoptive transfer protocols, longitudinal monitoring of cancer patients taking part in clinical trials is mandatory. Here, in vivo expansion of antigenspecific cells, as well as their ex vivo functional status represent important parameters to be analysed. To obtain results that most closely reflect the cells' in vivo status, functional assays must be carried out with as little in vitro culturing as possible. The present minireview discusses recent advances in these domains. Key words: cancer vaccines; T cell monitoring; tetramers; immunotherapy Tumour antigensRapid advances in the identification of MHC class I-restricted tumour antigens (TA) and their antigenic peptides 1 took place at the end of the 20th century, engendering antigen (Ag)-specific immunotherapy approaches to cancer treatment. [2][3][4] In contrast, progress in the molecular identification of MHC class II restricted peptides of TA has been much slower. Although tumour-specific CD8 ϩ T-cell responses have been documented upon vaccination with MHC class I-restricted peptides, it could be shown in murine tumour models that the generation of potent and long-lasting anti-tumour immunity is improved when both MHC class I-and class II-restricted T-cell epitopes are included in tumour vaccines. [5][6][7] These observations fostered the search for TA-derived peptides that are presented by class II molecules in cancer patients and lead to the isolation of diverse CD4 ϩ T-cell clones specific for given TA, though the precise epitopes have not yet been identified in all cases. 8,9 The high number of human MHC class II alleles severely limits the applicability of many of the antigenic peptides identified thus far. An exception is the HLA-DP4 molecule. Indeed, 2 highly prevalent alleles encode its ␤ chain and their combined frequency reaches approximately 60% of the population world-wide. Two HLA-DP4-restricted tumour associated antigenic peptides have been identified thus far. 10,11 Moreover, detailed analysis of HLA-DP4 peptide binding may facilitate future searches of novel tumour antigenic peptides restricted by this frequently occurring class II MHC allele. 12 Another favourable trait is the "degenerate" DR binding of certain antigenic peptides, i.e., various TA-derived antigenic peptides have been reported to bind to diverse HLA-DR molecules. 13,14 The identification of TA-derived epitopes presented by MHC class II molecules is complicated by the lack of effective screening methods. Recently, by combination of a computer-based algorithm for MHC-binding with T-cell functional analyses, a class II-restricted epitope of carcinoembryonic Ag (CEA, aa 116 -140) was identified that is naturally proce...

show abstract

HLA Class II-Restricted CD4+ T Cell Responses Directed Against Influenza Viral Antigens Postinfluenza Vaccination

Cited by 92 publications

References 34 publications

The heat shock protein Hsp70 enhances antigen-specific proliferation of human CD4+ memory T cells

The heat shock protein Hsp70 enhances antigen-specific proliferation of human CD4+ memory T cells

MHC class II Tetramer Guided Detection of Mycobacterium tuberculosis‐specific CD4⁺ T Cells in Peripheral Blood from Patients with Pulmonary Tuberculosis

Recent advances in tumour antigen‐specific therapy: In vivo veritas

Contact Info

Product

Resources

About

HLA Class II-Restricted CD4+ T Cell Responses Directed Against Influenza Viral Antigens Postinfluenza Vaccination

Cited by 92 publications

References 34 publications

The heat shock protein Hsp70 enhances antigen-specific proliferation of human CD4+ memory T cells

The heat shock protein Hsp70 enhances antigen-specific proliferation of human CD4+ memory T cells

MHC class II Tetramer Guided Detection of Mycobacterium tuberculosis‐specific CD4+ T Cells in Peripheral Blood from Patients with Pulmonary Tuberculosis

Recent advances in tumour antigen‐specific therapy: In vivo veritas

Contact Info

Product

Resources

About

MHC class II Tetramer Guided Detection of Mycobacterium tuberculosis‐specific CD4⁺ T Cells in Peripheral Blood from Patients with Pulmonary Tuberculosis