HLA-B51 transgenic mice as recipients for production of polymorphic HLA-A, B-specific antibodies

Karaki, Sachiko; Kariyone, Ai; Kato, Noriko; Kano, Kyoichi; Iwakura, Yoichiro; Takiguchi, Masafumi

doi:10.1007/bf00216838

Cited by 47 publications

(33 citation statements)

References 10 publications

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“…COS-7 and HSC-4 cells were used for the transfection. The human B lymphoblastoid cell line C1R, expressing a trace amount of HLA class I molecule and C1R-A*2402 [a HLA-A*2402 transfectant of C1R cells (14)] were used for peptidepulse experiments. The other cell lines used in this study were as follows: lung carcinoma (PC-9), esophageal carcinomas (TE3, TE9, TE11, and TE13), and head and neck carcinomas (HSC-4 and HSQ-89).…”

Section: Methodsmentioning

confidence: 99%

Identification of a Novel Human Cancer/Testis Antigen, KM-HN-1, Recognized by Cellular and Humoral Immune Responses

Monji

Nakatsura

Senju

et al. 2004

Clinical Cancer Research

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Purpose: We used serologic screening of a cDNA expression library of human testis to identify novel cancer/ testis antigens that elicit both humoral and cellular immune responses in cancer patients.Experimental Design and Results: We identified a novel gene designated KM-HN-1 the expression of which is testisspecific among normal tissues; it contains coiled coil domains and a leucine zipper motif and encodes a putative protein consisting of 833 amino acids. KM-HN-1 expression was observed in various cancer tissues and cancer cell lines at both mRNA and protein levels. Immunofluorescence staining of an esophageal cancer cell line revealed that KM-HN-1 protein was present exclusively in the nucleus during mitosis. Recombinant KM-HN-1 protein was produced, and used for ELISA to quantitate levels of IgG antibody specific to KM-HN-1. Higher levels of IgG antibodies specific to KM-HN-1 were detected in many types and numbers of cancer patients but not in healthy donors. The CTL lines specific to KM-HN-1, generated from HLA-A*2402-positive healthy donors and cancer patients, killed human leukocyte antigen (HLA)-A24-positive cancer cells expressing KM-HN-1 but not cell lines that did not express either KM-HN-1 or HLA-A24. Conclusions:We identified a novel cancer/testis antigen, KM-HN-1, which elicited humoral immune responses in patients with various types of cancer. Furthermore, KM-HN-1-specific CTLs could be generated from both healthy donors and cancer patients, which indicated that KM-HN-1 can be a candidate for an ideal target for cancer immunotherapy.

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Section: Methodsmentioning

confidence: 99%

Identification of a Novel Human Cancer/Testis Antigen, KM-HN-1, Recognized by Cellular and Humoral Immune Responses

Monji

Nakatsura

Senju

et al. 2004

Clinical Cancer Research

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“…C1R cells expressing HLA-A*1101 (C1R-A*1101) or HLA-A*0201 (C1R-A*0201) were previously generated (17) and were maintained in RPMI 1640 medium supplemented with 10% FCS and 0.15 mg/ml hygromycin B.…”

Section: Cellsmentioning

confidence: 99%

Three Memory Subsets of Human CD8+ T Cells Differently Expressing Three Cytolytic Effector Molecules

Takata

Takiguchi

2006

The Journal of Immunology

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143

150

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Multicolor flow cytometric analysis for the expression of three effector molecules, i.e., perforin (Per), granzyme A (GraA), and granzyme B (GraB), in human CD8+ T cells demonstrated that they included five subpopulations, implying the following pathway for the differentiation of CD8+ T cells: Per−GraA−GraB−→Per−GraA+GraB−→PerlowGraA+GraB−→ PerlowGraA+GraB+→PerhighGraA+GraB+. The analysis of the expression of these molecules in the subsets classified by the combination of the expression of CCR7 and CD45RA or by that of CD27, CD28, and CD45RA showed that functional CD8+ T cell subsets could be partially identified by these phenotypic classifications. However, the functional subsets could be precisely identified by the classification using five cell surface markers or three cell surface markers and three cytolytic molecules. Per−GraA−GraB− and Per−/lowGraA+GraB− cells were predominantly found in CCR5−CCR7+ and CCR5high/lowCCR7− subsets, respectively, of CD8+ T cells expressing the CD27+CD28+CD45RA− phenotype, whereas PerlowGraA+GraB+ cells were found in the CCR5lowCCR7− subset of those expressing this phenotype and in a part of the CCR5−/lowCCR7− subset of those expressing the CD27−/lowCD28−CD45RA−/+ phenotype. Ex vivo EBV-specific CD8+ T cells, which were Perlow/−GraA+GraB−/+ cells, hardly or very weakly killed the target cells, indicating that these were not effector T cells. These findings suggest that the Per−GraA−GraB−, Per−/lowGraA+GraB−, and PerlowGraA+GraB+ cells were central memory, early effector memory, and late effector memory T cells, respectively. Per−/lowGraA+GraB− cells gained GraB expression after TCR stimulation, indicating that early effector memory T cells could differentiate into late effector and effector T cells. The present study showed the existence of three memory subsets and the pathway for their differentiation.

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“…C1R cells expressing HLA-A*0201 (C1R-A*0201) were previously generated [28], and were maintained in RPMI 1640 medium supplemented with 10% FCS and 0.15 mg/ml hygromycin B. Two HLA-A*02-restricted, HCMV-1-specific CTL clones were recently established, and were maintained in RPMI 1640 medium supplemented with 10% FCS and 200 IU/ml r-human IL-2.…”

Section: Cellsmentioning

confidence: 99%

Phenotypic classification of human CD8⁺ T cells reflecting their function: inverse correlation between quantitative expression of CD27 and cytotoxic effector function

et al. 2004

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Phenotypic classification of human CD8 + T cells using three cell surface markers, CD27, CD28 and CD45RA, was recently suggested to be useful for identification of naive, memory and effector CD8 + T cells. However, it still remains unclear whether such classification precisely reflects functional classification of CD8 + T cells. To clarify this, we characterized each CD27CD28CD45RA subset of total and human cytomegalovirus (HCMV)-specific CD8 + T cells by analyzing the expression of perforin and two chemokine receptors, CCR5 and CCR7, as well as their function. An inverse correlation between perforin and CD27 expression was found in all four CD28CD45RA subsets. Therefore, to achieve a phenotypic classification of CD8 + T cells that more precisely reflects their function, the CD27 + subset was divided into CD27 low and CD27 high subsets based on the expression level of CD27. Functional and flow cytometric analyses of CD27CD28CD45RA subsets showed that this phenotypic classification reflects functional classification of CD8 + T cells. HCMV-specific CD8 + T cells from healthy HCMV-seropositive individuals were predominantly found in effector and memory/effector subsets, indicating that HCMV-specific effector CD8 + T cells are actively induced by HCMV replication in healthy HCMV carriers. Phenotypic analyses of CD8 + T cells using this classification will enable the characterization of antigen-specific CD8 + T cells.

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HLA-B51 transgenic mice as recipients for production of polymorphic HLA-A, B-specific antibodies

Cited by 47 publications

References 10 publications

Identification of a Novel Human Cancer/Testis Antigen, KM-HN-1, Recognized by Cellular and Humoral Immune Responses

Identification of a Novel Human Cancer/Testis Antigen, KM-HN-1, Recognized by Cellular and Humoral Immune Responses

Three Memory Subsets of Human CD8+ T Cells Differently Expressing Three Cytolytic Effector Molecules

Phenotypic classification of human CD8⁺ T cells reflecting their function: inverse correlation between quantitative expression of CD27 and cytotoxic effector function

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HLA-B51 transgenic mice as recipients for production of polymorphic HLA-A, B-specific antibodies

Cited by 47 publications

References 10 publications

Identification of a Novel Human Cancer/Testis Antigen, KM-HN-1, Recognized by Cellular and Humoral Immune Responses

Identification of a Novel Human Cancer/Testis Antigen, KM-HN-1, Recognized by Cellular and Humoral Immune Responses

Three Memory Subsets of Human CD8+ T Cells Differently Expressing Three Cytolytic Effector Molecules

Phenotypic classification of human CD8+ T cells reflecting their function: inverse correlation between quantitative expression of CD27 and cytotoxic effector function

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Phenotypic classification of human CD8⁺ T cells reflecting their function: inverse correlation between quantitative expression of CD27 and cytotoxic effector function