Comprehensive typing of DR52 (DRB3)‐associated DRB1 and DRB3 alleles by PCR‐RFLP

Sengar, D. P. S.; Goldstein, Rose; Toye, Baldwin; Hampton, N.

doi:10.1111/j.1399-0039.1994.tb02342.x

Cited by 11 publications

(8 citation statements)

References 25 publications

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“…These genes have strong linkage disequilibrium with defined DRB1 alleles. In particular, DR52 is very frequently expressed in the population, as DRB3 alleles are associated through linkage disequilibrium to some of the most common DRB1 alleles (20). Lower expression and linkage disequilibrium with DRB1 alleles may account for the fact that T cell epitopes restricted by these alternate DR molecules have been described less frequently than those restricted by DRB1-encoded molecules, or have been reported as restricted by the associated DRB1 allele.…”

Section: Resultsmentioning

confidence: 99%

Vaccination with Recombinant NY-ESO-1 Protein Elicits Immunodominant HLA-DR52b-restricted CD4+ T Cell Responses with a Conserved T Cell Receptor Repertoire

Bioley

Dousset

Yeh

et al. 2009

Clinical Cancer Research

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Purpose: ESO is a tumor-specific antigen with wide expression in human tumors of different histologic types and remarkable spontaneous immunogenicity. We have previously shown that specific T H 1 and antibody responses can be elicited in patients with no detectable preexisting immune responses by vaccination with rESO administered with Montanide ISA-51 and CpG ODN 7909. The purpose of the present study was to characterize vaccine-induced ESO-specific CD4 + Tcell responses. Experimental Design: We generated CD4 + T cell clones from patient C2, who had the highest CD4 + Tcell response to the vaccine, and analyzed their fine specificity and HLA class II restriction to determine the recognized epitope.We then assessed the response to the identified epitope in all vaccinated patients expressing the corresponding HLA class II allele. Results: We found that ESO-specific CD4 + T cell clones from patient C2 recognize peptide ESO 119-143 (core region 123-137) presented by HLA-DR52b (HLA-DRB3*0202), a MHC class II allele expressed by about half of Caucasians. Importantly, following vaccination, all patients expressing DR52b developed significant responses to the identified epitope, accounting for, on average, half of the total CD4 + T cell responses to the 119-143 immunodominant region. In addition, analysis of ESO-specific DR52b-restricted CD4 + T cells at the clonal level revealed significant conservation of T cell receptor usage among different individuals. Conclusions: The identification of a DR52b-restricted epitope from ESO that is immunodominant in the context of vaccine-elicited immune responses is instrumental for the immunologic monitoring of vaccination trials targeting this important tumor antigen.

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Section: Resultsmentioning

confidence: 99%

Vaccination with Recombinant NY-ESO-1 Protein Elicits Immunodominant HLA-DR52b-restricted CD4+ T Cell Responses with a Conserved T Cell Receptor Repertoire

Bioley

Dousset

Yeh

et al. 2009

Clinical Cancer Research

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“…Whereas DRB1 is present in all individuals, DRB3, DRB4, and DRB5 are only present in some of them, and are in strong linkage disequilibrium with defined DRB1 alleles. These alternate DR molecules are generally expressed at lower levels when compared with those encoded by DRB1, but are fully functional with respect to antigen presentation (13,23,24). These molecules are less polymorphic than DRB1-encoded molecules and therefore represent ideal candidates for the generation of generic class II tetramers (25).…”

Section: Discussionmentioning

confidence: 99%

Monitoring of NY-ESO-1 specific CD4 ⁺ T cells using molecularly defined MHC class II/His-tag-peptide tetramers

Ayyoub

Dojcinovic

Pignon

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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MHC-peptide tetramers have become essential tools for T-cell analysis, but few MHC class II tetramers incorporating peptides from human tumor and self-antigens have been developed. Among limiting factors are the high polymorphism of class II molecules and the low binding capacity of the peptides. Here, we report the generation of molecularly defined tetramers using His-tagged peptides and isolation of folded MHC/peptide monomers by affinity purification. Using this strategy we generated tetramers of DR52b (DRB3*0202), an allele expressed by approximately half of Caucasians, incorporating an epitope from the tumor antigen NY-ESO-1. Molecularly defined tetramers avidly and stably bound to specific CD4 + T cells with negligible background on nonspecific cells. Using molecularly defined DR52b/ NY-ESO-1 tetramers, we could demonstrate that in DR52b + cancer patients immunized with a recombinant NY-ESO-1 vaccine, vaccineinduced tetramer-positive cells represent ex vivo in average 1:5,000 circulating CD4 + T cells, include central and transitional memory polyfunctional populations, and do not include CD4 + CD25 + CD127 − regulatory T cells. This approach may significantly accelerate the development of reliable MHC class II tetramers to monitor immune responses to tumor and self-antigens.S oluble MHC-peptide tetramers, allowing the direct visualization, characterization, and isolation of antigen-specific T cells, have become essential tools for T-cell analysis. MHC class I tetramers incorporating short CTL peptide epitopes, originally developed by Altman and Davis (1) have been generated for a large number of murine and human alleles, incorporating a variety of peptides of microbial, tumor, and self-antigen origin (2). The development of MHC class II tetramers, however, and particularly of those incorporating peptides from tumor and self-antigens, has been far less successful (3-5). One limiting factor is the high polymorphism of the human MHC class II molecules, especially those encoded by the DRB1 locus, the most frequently studied. Another limiting factor is the binding affinity of antigenic peptides derived from tumor and self-antigens, which is generally lower than that of peptides from pathogens.NY-ESO-1 (ESO), a tumor-specific antigen of the cancer/testis group frequently expressed in tumors of different histological types (6), is an important candidate for the development of generic cancer vaccines (7). In a recent vaccination trial using a recombinant ESO protein (rESO) administered with Montanide ISA 51 and CpG ODN 7909, we have observed induction of CD4 + T cell responses in all vaccinated patients (8). By assessing vaccineinduced CD4 + T cells, we have identified an immunodominant epitope , core region ESO 123-137 ) restricted by HLADR52b (DRB3*0202), an allele expressed by half of Caucasians (9). DRB3-, DRB4-, and DRB5-encoded molecules are less polymorphic than those encoded by DRB1, and are therefore attractive candidates for the development of generic MHC class II tetramers.Our initial attempts to const...

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“…Regarding the DRB I-DR52 alleles, different typing methods have been attempted (Shaffer. et al, 1992;El-Borai, 1993;Sengar et al, 1994). In particular, SSCP analysis of the DRII group of alleles has been described by Kimura etal.…”

Section: Introductionmentioning

confidence: 96%

Single‐strand Conformation Polymorphism (Sscp) Analysis of Hla‐drb1*1101‐06

Mora

Petronzelli

Grillo

et al. 1996

Int J Immunogenetics

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Single-strand conformation polymorphism (SSCP) has been developed as a method for detecting the presence of mutations in a segment of DNA. We applied it to the subtyping of the DRII group of alleles. The SSCP patterns of DRB I-DR52 group-specific products were defined in cell lines representing the DRBI*1101-06 alleles, using non-denaturing acrylamide gel electrophoresis and silver staining. Only one set of gel electrophoresis conditions was able to discriminate the DRII alleles tested. The protocol was validated in an analysis of 105 DRll-positive individuals previously typed by oligonucleotides probing. The study demonstrates the suitability of the SSCP technique to define the DRB 1*1101-06 alleles, the technique being particularly valuable in confirming and extending the oligotyping of DRBI-DR52 heterozygous samples.analysis and heteroduplex analysis (Sorrentino et al., 1992;D' Amato & Sorrentino, 1994;Savage et al., 1995). SSCP is based on the different mobilities of DNA single strands in non-denaturing electrophoresis conditions, depending on their sequences and, consequently, on the secondary structures they assume during the migration (Orita et al., 1989). This powerful technique allows the discrimination of a single mutation in a fragment of DNA under the right conditions, even if it is not able to define its

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Comprehensive typing of DR52 (DRB3)‐associated DRB1 and DRB3 alleles by PCR‐RFLP

Cited by 11 publications

References 25 publications

Vaccination with Recombinant NY-ESO-1 Protein Elicits Immunodominant HLA-DR52b-restricted CD4+ T Cell Responses with a Conserved T Cell Receptor Repertoire

Vaccination with Recombinant NY-ESO-1 Protein Elicits Immunodominant HLA-DR52b-restricted CD4+ T Cell Responses with a Conserved T Cell Receptor Repertoire

Monitoring of NY-ESO-1 specific CD4 ⁺ T cells using molecularly defined MHC class II/His-tag-peptide tetramers

Single‐strand Conformation Polymorphism (Sscp) Analysis of Hla‐drb1*1101‐06

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Comprehensive typing of DR52 (DRB3)‐associated DRB1 and DRB3 alleles by PCR‐RFLP

Cited by 11 publications

References 25 publications

Vaccination with Recombinant NY-ESO-1 Protein Elicits Immunodominant HLA-DR52b-restricted CD4+ T Cell Responses with a Conserved T Cell Receptor Repertoire

Vaccination with Recombinant NY-ESO-1 Protein Elicits Immunodominant HLA-DR52b-restricted CD4+ T Cell Responses with a Conserved T Cell Receptor Repertoire

Monitoring of NY-ESO-1 specific CD4 + T cells using molecularly defined MHC class II/His-tag-peptide tetramers

Single‐strand Conformation Polymorphism (Sscp) Analysis of Hla‐drb1*1101‐06

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Monitoring of NY-ESO-1 specific CD4 ⁺ T cells using molecularly defined MHC class II/His-tag-peptide tetramers