Topic
Antigen
About: Antigen is a research topic. Over the lifetime, 170233 publications have been published within this topic receiving 6982342 citations. The topic is also known as: antibody generator & Antigen.
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TL;DR: In patients who do respond to the vaccine, the antivaccine T cells probably succeed in reversing focally this immunosuppression and trigger a broad activation of other antitumor T cells, which proceed to destroy the tumor.
Abstract: Many antigens recognized by autologous T lymphocytes have been identified on human melanoma. Melanoma patients usually mount a spontaneous T cell response against their tumor. But at some point, the responder T cells become ineffective, probably because of a local immunosuppressive process occurring at the tumor sites. Therapeutic vaccination of metastatic melanoma patients with these antigens is followed by tumor regressions only in a small minority of the patients. The T cell responses to the vaccines show correlation with the tumor regressions. The local immunosuppression may be the cause of the lack of vaccination effectiveness that is observed in most patients. In patients who do respond to the vaccine, the antivaccine T cells probably succeed in reversing focally this immunosuppression and trigger a broad activation of other antitumor T cells, which proceed to destroy the tumor.
652 citations
TL;DR: Findings indicate a possible molecular basis for this HLA-disease association and support the candidacy of liver-stage-specific antigen-1 as a malaria vaccine component.
Abstract: The protective association between the human leukocyte antigen HLA-B53 and severe malaria was investigated by sequencing of peptides eluted from this molecule followed by screening of candidate epitopes from pre-erythrocytic-stage antigens of Plasmodium falciparum in biochemical and cellular assays. Among malaria-immune Africans, HLA-B53-restricted cytotoxic T lymphocytes recognized a conserved nonamer peptide from liver-stage-specific antigen-1 (LSA-1), but no HLA-B53-restricted epitopes were identified in other antigens. These findings indicate a possible molecular basis for this HLA-disease association and support the candidacy of liver-stage-specific antigen-1 as a malaria vaccine component.
652 citations
TL;DR: Analysis of activation of naive proteolipid protein (PLP)139–151-specific T cells in SJL mice undergoing PLP178–191-induced R-EAE or TMEV-IDD suggests that naive T cells enter the inflamed CNS and are activated by local APCs, possibly DCs, to initiate epitope spreading.
Abstract: Chronic progression of two T cell–mediated central nervous system (CNS) demyelinating models of multiple sclerosis, relapsing EAE (R-EAE) and Theiler's murine encephalomyelitis virus–induced demyelinating disease (TMEV-IDD) is dependent on the activation of T cells to endogenous myelin epitopes (epitope spreading). Using transfer of carboxyfluorescein succinyl ester (CFSE)-labeled T-cell receptor (TCR)-transgenic T cells and mixed bone marrow chimeras, we show that activation of naive proteolipid protein (PLP)139–151-specific T cells in SJL mice undergoing PLP178–191-induced R-EAE or TMEV-IDD occurs directly in the CNS and not in the cervical lymph nodes or other peripheral lymphoid organs. Examination of the antigen-presentation capacity of antigen-presenting cell (APC) populations purified from the CNS of mice with PLP178–191-induced R-EAE shows that only F4/80−CD11c+CD45hi dendritic cells (DCs) efficiently present endogenous antigen to activate naive PLP139–151-specific T cells in vitro. In contrast, DCs as well as F4/80+CD45hi macrophages and F4/80+CD45lo microglia activate a PLP139–151-specific helper T cell line. The data suggest that naive T cells enter the inflamed CNS and are activated by local APCs, possibly DCs, to initiate epitope spreading.
652 citations
TL;DR: Human IEC lines secrete exosomes bearing accessory molecules that may be involved in antigen presentation consistent with a model in which IECs may influence antigen presentation in the mucosal or systemic immune system independent of direct cellular contact with effector cells.
652 citations
TL;DR: It is shown that tumor-derived virus mutations do not affect retinoblastoma tumor suppressor protein (Rb) binding by LT but do eliminate viral DNA replication capacity, suggesting that MCV-positive MCC tumor cells undergo selection for LT mutations to prevent autoactivation of integrated virus replication that would be detrimental to cell survival.
Abstract: Merkel cell polyomavirus (MCV) is a virus discovered in our laboratory at the University of Pittsburgh that is monoclonally integrated into the genome of ≈80% of human Merkel cell carcinomas (MCCs). Transcript mapping was performed to show that MCV expresses transcripts in MCCs similar to large T (LT), small T (ST), and 17kT transcripts of SV40. Nine MCC tumor-derived LT genomic sequences have been examined, and all were found to harbor mutations prematurely truncating the MCV LT helicase. In contrast, four presumed episomal viruses from nontumor sources did not possess this T antigen signature mutation. Using coimmunoprecipitation and origin replication assays, we show that tumor-derived virus mutations do not affect retinoblastoma tumor suppressor protein (Rb) binding by LT but do eliminate viral DNA replication capacity. Identification of an MCC cell line (MKL-1) having monoclonal MCV integration and the signature LT mutation allowed us to functionally test both tumor-derived and wild type (WT) T antigens. Only WT LT expression activates replication of integrated MCV DNA in MKL-1 cells. Our findings suggest that MCV-positive MCC tumor cells undergo selection for LT mutations to prevent autoactivation of integrated virus replication that would be detrimental to cell survival. Because these mutations render the virus replication-incompetent, MCV is not a “passenger virus” that secondarily infects MCC tumors.
651 citations