HLA class II restriction repertoire of antigen-specific T cells. I. The main restriction determinants for antigen presentation are associated with HLA-D/DR and not with DP and DQ

Ottenhoff, Tom H. M.; Elferink, Diënne G.; Hermans, J.; Vries, RenéR.P. de

doi:10.1016/0198-8859(85)90017-5

Cited by 75 publications

(29 citation statements)

References 23 publications

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“…Each peptide was recognized by at least one T-cell line. T-cell lines that were raised from the PBMC of TB patients with similar HLA-DR phenotypes tended to recognize the same (20). Dose-response curves for rESAT-6, rCFP-10, and the corresponding peptide mixtures indicated that the optimal concentrations were similar for the recombinant antigens and the peptides in the mixture.…”

Section: T-cell Responses To Individual Peptides Of Esat-6 and Cfp-10mentioning

confidence: 87%

“…T-cell lines were generated as previously described (20). Briefly, PBMC obtained from TB patients or control subjects were incubated at 1 to 2 million cells per well in 24-well plates (Nunc, Roskilde, Denmark) in the presence of M. tuberculosis H37Rv sonicate or ST-CF at 5 g/ml for 6 days and then expanded with recombinant interleukin-2; this was followed by freezing of the T-cell lines and storage in liquid nitrogen.…”

Section: Methodsmentioning

confidence: 99%

“…The known association of HLA-DR2 with TB (8,22) prompted us to examine whether T-cell responses to rESAT-6 and rCFP-10 segregate according to HLA-DR type, which is quantitatively the most important class II antigen-presenting molecule (20), with a focus on HLA-DR2. All HLA-DR types were represented in the population of TB patients in this study, half of whom were immigrants from various regions of origin.…”

Section: T-cell Responses To Individual Peptides Of Esat-6 and Cfp-10mentioning

confidence: 99%

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Antigenic Equivalence of Human T-Cell Responses to Mycobacterium tuberculosis -Specific RD1-Encoded Protein Antigens ESAT-6 and Culture Filtrate Protein 10 and to Mixtures of Synthetic Peptides

et al. 2000

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The early secreted antigenic target 6-kDa protein (ESAT-6) and culture filtrate protein 10 (CFP-10) are promising antigens for reliable immunodiagnosis of tuberculosis. Both antigens are encoded by RD1, a genomic region present in all strains of Mycobacterium tuberculosis and M. bovis but lacking in all M. bovis bacillus Calmette-Guérin vaccine strains. Production and purification of recombinant antigens are laborious and costly, precluding rapid and large-scale testing. Aiming to develop alternative diagnostic reagents, we have investigated whether recombinant ESAT-6 (rESAT-6) and recombinant CFP-10 (rCFP-10) can be replaced with corresponding mixtures of overlapping peptides spanning the complete amino acid sequence of each antigen. Proliferation of M. tuberculosis-specific human T-cell lines in response to rESAT-6 and rCFP-10 and that in response to the corresponding peptide mixtures were almost completely correlated (r ‫؍‬ 0.96, P < 0.0001 for ESAT-6; r ‫؍‬ 0.98, P < 0.0001 for CFP-10). More importantly, the same was found when gamma interferon production by peripheral blood mononuclear cells in response to these stimuli was analyzed (r ‫؍‬ 0.89, P < 0.0001 for ESAT-6; r ‫؍‬ 0.89, P < 0.0001 for CFP-10). Whole protein antigens and the peptide mixtures resulted in identical sensitivity and specificity for detection of infection with M. tuberculosis. The peptides in each mixture contributing to the overall response varied between individuals with different HLA-DR types. Interestingly, responses to CFP-10 were significantly higher in the presence of HLA-DR15, which is the major subtype of DR2. These results show that mixtures of synthetic overlapping peptides have potency equivalent to that of whole ESAT-6 and CFP-10 for sensitive and specific detection of infection with M. tuberculosis, and peptides have the advantage of faster production at lower cost.Tuberculosis (TB) accounts for several million deaths per year worldwide. The synergism between infection with the human immunodeficiency virus and Mycobacterium tuberculosis (4, 12), combined with the emergence of multidrug-resistant strains of M. tuberculosis in several parts of the world (11) have fueled fears of the spread of TB in the near future (5). Next to an improved vaccine, the development of a rapid and reliable diagnostic assay for early detection of TB is a high priority. The available tuberculin (purified protein derivative [PPD]) skin test has a high frequency of false-positive results after previous vaccination with M. bovis bacillus Calmette-Guérin (BCG) (15), and nowadays more than half of all newly detected cases of TB in The Netherlands and other industrialized countries occur among immigrants from regions where TB is highly endemic and BCG vaccination is routinely used. In addition, false-negative PPD skin test results occur in patients with advanced TB (15). Comparative genomics is a relatively recent field of research that has contributed importantly to the identification of M. tuberculosis-specific antigens. Subtractive DNA hybridization...

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Section: T-cell Responses To Individual Peptides Of Esat-6 and Cfp-10mentioning

confidence: 87%

Section: Methodsmentioning

confidence: 99%

Section: T-cell Responses To Individual Peptides Of Esat-6 and Cfp-10mentioning

confidence: 99%

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Antigenic Equivalence of Human T-Cell Responses to Mycobacterium tuberculosis -Specific RD1-Encoded Protein Antigens ESAT-6 and Culture Filtrate Protein 10 and to Mixtures of Synthetic Peptides

et al. 2000

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“…HLA-DRB polymorphism plays an important regulatory role in controlling human T-cell reactivity against mycobacteria (20,21). Previously, we demonstrated that the 15-mer Rv1733c p63-77 epitope was immunogenic in vivo either alone or as part of an HLA-DR3-restricted multistage polyepitope.…”

Section: Identification Of M Tuberculosis Antigens That Induce Dendrmentioning

confidence: 99%

“…Our previous work has shown that HLA-DRB polymorphism controls human T-cell responsiveness (20). In this respect, HLA-DR3, a major class II allele that is present in 20% of the human population, is associated with strong T-cell activity to mycobacterial Ags, in vitro and in vivo, and with high-responder (tuberculoid) leprosy (21).…”

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confidence: 99%

Synthetic Long Peptide Derived from Mycobacterium tuberculosis Latency Antigen Rv1733c Protects against Tuberculosis

Coppola

Eeden

Wilson

et al. 2015

Clin Vaccine Immunol

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Despite the availability of a vaccine and chemotherapeutic agents, tuberculosis (TB) remains the second leading cause of death from an infectious disease worldwide, annually causing around 9 million new cases and almost 2 million deaths (1). The highest burdens are found in low-income regions: Africa harbors about 25% of the world's TB cases and more than half have been counted in Asia (1). Furthermore, surveys with tuberculin skin tests (TST) suggest that one-third of the world's population is latently infected with Mycobacterium tuberculosis, which constitutes a huge reservoir with a 3 to 10% lifetime risk of developing TB (1, 2).It has long been recognized that the efficacy of vaccination with Mycobacterium bovis BCG, still the only registered TB vaccine, can be enhanced by a booster or replacement vaccine protecting against reactivating TB from latency (3). M. tuberculosis latency antigens (Ags), encoded by the DosR regulon, are upregulated in vitro under conditions that tubercle bacilli are thought to encounter in vivo during persistence in immunocompetent hosts (4) and in mouse models for latent M. tuberculosis infection (LTBI) (5). This discovery caused a change in focus in the search for a novel antigen(s) able to enhance long-term vaccine efficacy. Various human cohort studies showed preferential recognition of DosRencoded proteins, in particular Rv1733c, Rv2029c, Rv2627c, and Rv2628, by T cells from individuals with LTBI and to a lesser extent by TB patients (6-9). Also, latency antigens can induce CD4 ϩ and CD8 ϩ T cells in TST-converted individuals who were infected with M. tuberculosis decades ago in the preantibiotic era and yet never developed TB (10, 11).In mouse models using chronic, low-dose M. tuberculosis infection mimicking human LTBI, the preferential recognition of the DosR regulon in latent infection was further established (5) and provided evidence that BCG fails to induce a significant response to latency antigens despite their presence in the BCG genome. Also, a triple fusion protein, designated H56, including the latency/starvation antigen Rv2660 coupled to the early-stage proteins Ag85B and ESAT-6, provided protection by both pre-and postinfection vaccination in nonhuman primates (12,13). A similar improvement in long-term protection against M. tuberculosis was observed in mice after intradermal inoculation of recombinant BCG expressing the latency-associated antigens Rv2659c, Rv3407, and Rv1733c (14).Synthetic long peptides (SLPs), administered with adjuvants, are proven efficient vaccines for tumor therapy (15)(16)(17)(18)(19). Despite the success of this vaccine strategy, SLPs have not yet been applied to design new TB vaccines. Recognition of cognate antigen presented by either T cells or B cells will lead to an abortive proliferative response and death of the responding T cells.The immunogenicity of Rv1733c, which was the most commonly recognized latency antigen in M. tuberculosis-exposed household contacts from South Africa, Gambia, and Uganda (9), as well as the improved long...

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Quantitative and qualitative differences in HLA‐DR molecules correlated with antigen‐presentation capacity

Bontrop

Ottenhoff

et al. 1986

Eur J Immunol

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The monoclonal antibodies 7.3.19.1 (anti-DRw52-like) and B8.11.2 (anti-DR framework) were used for the isolation and characterization of HLA class II molecules expressed by HLA-DR3 and DR5 homozygous B cell lines. Sequential immunoprecipitation studies demonstrated that from these cells class II molecules can be isolated which are characterized by the presence or absence of DR framework (DR) and DRw52-like (DRw62) determinants: (DR+, DRw52+), (DR+, DRw52-) and (DR-, DRw52+). The DR3 donor cells appeared to express only the (DR+, DRw52+) and (DR-, DRw52+) class II molecules whereas DR5-positive cells express only the (DR+, DRw52+) and (DR+, DRw52-) class II molecules. Besides qualitative differences some of the above-mentioned molecules appeared to differ in their levels of expression. To investigate whether this might have functional implications, cells with the HLA-DR3 and -5 haplotypes were used to present antigen purified protein derivative of tuberculin (PPD) to PPD-specific T cell lines and the blocking capacity of the two monoclonal antibodies 7.3.19.1 and B8.11.2 was determined. A remarkable correlation was observed between the type of class II molecule blocked by these monoclonal antibodies and its quantitative expression. However, (DR-, DRw52+) molecules, clearly expressed by DR3 cells, were not involved in the presentation of PPD. This indicates that not only quantitative but also qualitative aspects may play a role in the selection of the type of class II molecule that will be involved in antigen presentation.

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HLA class II restriction repertoire of antigen-specific T cells. I. The main restriction determinants for antigen presentation are associated with HLA-D/DR and not with DP and DQ

Cited by 75 publications

References 23 publications

Antigenic Equivalence of Human T-Cell Responses to Mycobacterium tuberculosis -Specific RD1-Encoded Protein Antigens ESAT-6 and Culture Filtrate Protein 10 and to Mixtures of Synthetic Peptides

Antigenic Equivalence of Human T-Cell Responses to Mycobacterium tuberculosis -Specific RD1-Encoded Protein Antigens ESAT-6 and Culture Filtrate Protein 10 and to Mixtures of Synthetic Peptides

Synthetic Long Peptide Derived from Mycobacterium tuberculosis Latency Antigen Rv1733c Protects against Tuberculosis

Quantitative and qualitative differences in HLA‐DR molecules correlated with antigen‐presentation capacity

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