Use of HLA-B27 tetramers to identify low-frequency antigen-specific T cells in Chlamydia-triggered reactive arthritis

Reports of the use of HLA-B27/peptide tetrameric complexes to study peptide-specific CD8(+ )T cells in HLA-B27(+)-related diseases are rare. To establish HLA-B27 tetramers we first compared the function of HLA-B27 tetramers with HLA-A2 tetramers by using viral epitopes. HLA-B27 and HLA-A2 tetramers loaded with immunodominant peptides from Epstein–Barr virus were generated with comparable yields and both molecules detected antigen-specific CD8(+ )T cells. The application of HLA-B27 tetramers in HLA-B27-related diseases was performed with nine recently described Chlamydia-derived peptides in synovial fluid and peripheral blood, to examine the CD8(+ )T cell response against Chlamydia trachomatis antigens in nine patients with Chlamydia-triggered reactive arthritis (Ct-ReA). Four of six HLA-B27(+ )Ct-ReA patients had specific synovial T cell binding to at least one HLA-B27/Chlamydia peptide tetramer. The HLA-B27/Chlamydia peptide 195 tetramer bound to synovial T cells from three of six patients and HLA-B27/Chlamydia peptide 133 tetramer to synovial T cells from two patients. However, the frequency of these cells was low (0.02–0.09%). Moreover, we demonstrate two methods to generate HLA-B27-restricted T cell lines. First, HLA-B27 tetramers and magnetic beads were used to sort antigen-specific CD8(+ )T cells. Second, Chlamydia-infected dendritic cells were used to stimulate CD8(+ )T cells ex vivo. Highly pure CD8 T cell lines could be generated ex vivo by magnetic sorting by using HLA-B27 tetramers loaded with an EBV peptide. The frequency of Chlamydia-specific, HLA-B27 tetramer-binding CD8(+ )T cells could be increased by stimulating CD8(+ )T cells ex vivo with Chlamydia-infected dendritic cells. We conclude that HLA-B27 tetramers are a useful tool for the detection and expansion of HLA-B27-restricted CD8(+ )T cells. T cells specific for one or more of three Chlamydia-derived peptides were found at low frequency in synovial fluid from HLA-B27(+ )patients with Ct-ReA. These cells can be expanded ex vivo, suggesting that they are immunologically functional

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Asynchronicity and Learning in Cost Sharing Mechanisms

This paper reports the first experimental study of the serial and the average cost pricing mechanism under three different treatments: a complete information treatment and two treatments designed to simulate distributed systems like the internet with extremely limited information, synchronous and asynchronous moves. Under the complete information treatment both mechanisms converge well to the Nash equilibrium prediction and their performance are statistically indistinguishable. Under the limited information treatments, however, the serial mechanism consistently outperforms the average cost pricing mechanism. With exactly the same amount of information as required by reinforcement learning algorithms, a much higher proportion of experimental subjects converged to the equilibrium much faster than predicted by reinforcement learning model. I am indebted to Scott Shenker for his many helpful comments and suggestions. I thank Lutz Kilian, Bettina Kuon, Wolfgang Lorenzon, Richard McKelvey, ..

Kaposi's Sarcoma-Associated Herpesvirus Cytotoxic T Lymphocytes Recognize and Target Darwinian Positively Selected Autologous K1 Epitopes

Kaposi's sarcoma-associated herpesvirus (KSHV) is the infectious cause of Kaposi's sarcoma (KS) and certain lymphoproliferations particularly in the context of human immunodeficiency virus (HIV) type 1-induced immunosuppression. The introduction of effective therapies to treat HIV has led to a decline in the incidence of KS, suggesting that immune responses may play a role in controlling KSHV infection and pathogenesis. Cytotoxic-T-lymphocyte (CTL) activity against KSHV proteins has been demonstrated; however, the identification of KSHV CTL epitopes remains elusive and problematic. Although the herpesvirus genomic layout is generally conserved, KSHV encodes a unique hypervariable protein, K1, with intense biological selection pressure at specific amino acid sites. To investigate whether this variability is partly driven by cellular immunity, we designed K1 peptides that match only the unique viral sequence for every individual studied here (autologous peptides). We identified functional CTL epitopes within K1's most variable areas, and we show that a given individual responds only to autologous peptides and not to peptides from other individuals. Furthermore, these epitopes are highly conserved sequences within KSHV isolates from a specific strain but are not conserved between different strains. We conclude that CTL recognition contributes to K1, and therefore to KSHV, evolution

Recurrent Miscarriage: Diagnostic and Therapeutic Procedures. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry Number 015/050).

Purpose Official guideline of the German Society of Gynecology and Obstetrics (DGGG), the Austrian Society of Gynecology and Obstetrics (ÖGGG) and the Swiss Society of Gynecology and Obstetrics (SGGG). The aim of this guideline was to standardize the diagnosis and treatment of couples with recurrent miscarriage (RM). Recommendations were based on the current literature and the views of the involved committee members. Methods Based on the current literature, the committee members developed the statements and recommendations of this guideline in a formalized process which included DELPHI rounds and a formal consensus meeting. Recommendations Recommendations for the diagnosis and treatment of patients with RM were compiled based on the international literature. Specific established risk factors such as chromosomal, anatomical, endocrine, hemostatic, psychological, infectious and immunological disorders were taken into consideration