Biomedical subjects

Jane H Buckner

Publications and source records attributed to Jane H Buckner.

6 recordsLinked to original sources

PubMed2002

Use of class II tetramers for identification of CD4+ T cells.

Multivalent MHC class II molecules containing peptide antigens are useful tools for the detection of antigen specific human CD4+ T cells. Tetramers produced by exogenous peptide loading onto empty class II molecules are comparable to tetramers with peptide tethered to the class II chain covalently, but have many practical advantages. Conditions for optimal peptide loading to generate tetramers are discussed and optimal conditions of using tetramers for staining T cells are examined. As the frequency of antigen specific CD4+ T cells in peripheral blood is low, we demonstrate that an in vitro expansion step is effective in detecting low frequency T cells. Two new applications with tetramers, their uses for mapping T cell epitopes and for the detection of low affinity T cells are described. In a clinical setting, potential applications include using these reagents for monitoring disease progression during clinical intervention.

Animals↗

PubMed2002

Identification of type II collagen peptide 261-273-specific T cell clones in a patient with relapsing polychondritis.

OBJECTIVE: To characterize and clone T cells specific for type II collagen (CII) in a patient with relapsing polychondritis (RP) and to establish whether the immunodominant epitope of CII determined in HLA transgenic mice is used in the human autoimmune response to CII. METHODS: T cell responses to CII were examined in a patient with RP, who was heterozygous for the HLA-DR allele DRB1*0101/DRB1*0401. T cell clones were established from this patient and characterized for peptide specificity, class II restriction, cytokine production, and staining with HLA-DRB1*0401 class II tetramers. RESULTS: A response to CII and the peptide 255-273 was present in this patient. T cells specific for the CII epitope 261-273 were cloned. Evaluation of these clones demonstrated a response to CII 261-273 in the context of both DR alleles. HLA-DR4 CII tetramer did not demonstrate staining of either CII-specific DRB1*0401-restricted T cell clones or a polyclonal population of CII-reactive T cells from this individual. CONCLUSION: T cells directed against CII were present in this patient with RP. Also, T cell clones isolated from this individual were found to be specific for the CII peptide 261-273 and were restricted to either the DRB1*0101 or the DRB1*0401 allele. These findings establish that a T cell response directed against CII is present in this patient with RP and that the CII peptide 261-273 plays a role in the human immune response to CII.

Adult↗

PubMed2002

HLA class II tetramers: tools for direct analysis of antigen-specific CD4+ T cells.

Immunotherapies for human autoimmune and immune-mediated diseases are proliferating rapidly, and with these changes comes the opportunity to monitor patients for immune responses to therapy based on early surrogate markers for clinical responses. Class II tetramers have the potential to serve as these sorts of markers for immune monitoring, and thereby assist with patient management, therapy selection, and improved outcomes. However, important issues of TCR avidity require resolution, because much is still unknown regarding location, quantitation, and characterization of the human T cell response. Opportunities for application of tetramer technologies in the near future will enable both clinical progress and the development of new insights into human CD4+ T cell biology in vivo.

CD4-Positive T-Lymphocytes↗

PubMed2002

Transcript array analysis in rheumatology.

Transcript array analysis is a novel technique that examines the expression of thousands of genes simultaneously. Transcript array analyses are being used to clarify the diagnosis and prognosis of malignancies, and to understand the underlying pathogenesis of complex human disorders such as the rheumatic diseases. In this review, the authors will outline the use of transcript arrays to simultaneously assess gene activation of hundreds or thousands of genes, and their potential use in understanding and managing rheumatic disorders. The authors focus on the use of transcript arrays to confirm and refine disease diagnoses, to generate new hypotheses regarding pathophysiology of rheumatic diseases, and to the possible profiling of patients with respect to their likely response to therapies.

Animals↗

PubMed2002

Defining antigen-specific responses with human MHC class II tetramers.

Antigen-specific CD4(+) T lymphocytes play key roles in the orchestration of immune responses, including the initiation and amplification of allergic and immune-mediated disorders. Direct detection and quantitation of these cells is made possible by the use of HLA class II tetramers, soluble recombinant forms of a complex of HLA molecule and antigenic peptide that bind the antigen-specific T-cell receptor used for T-cell recognition. By using flow cytometry with fluorescent tetramers, specific T cells can be identified, recovered, and analyzed for functional markers and transcripts, helping to characterize the lineage and commitment program for individual lymphocytes. Several newly emerging uses for tetramers in clinical immunology are under development for patient management or prognosis when the number or nature of antigen-specific T cells can be clinically important. Tetramers might be useful as patient-monitoring tools for evaluating response to immunotherapy, providing a surrogate marker for the immunologic response foreshadowing a clinical response to either immune stimulation, suppression, or deviation therapeutic modalities.

Antigens↗

PubMed2002

Genetics of rheumatoid arthritis: is there a scientific explanation for the human leukocyte antigen association?

Human leukocyte antigen genes associated with rheumatoid arthritis are commonly found in the unaffected population, implying that causal mechanisms of disease involve interactions between these genes and other factors. A variety of approaches-genetic, structural, and immunologic-are used to explore possible molecular interactions that may contribute to understanding the basis for this disease association. The specific relation between human leukocyte antigen-DR4 alleles and rheumatoid arthritis remains one of the strongest and most thoroughly studied examples of human leukocyte antigen risk genes among human autoimmune disorders.

Alleles↗