The Inducible System: Antigens
Julius P. Kreier in Infection, Resistance, and Immunity, 2022
An antigen was originally considered simply to be any substance capable of inducing the generation of antibody. In fact, the word antigen was coined from the words “antibody” and “generator.” Cross-reactivity may thus be the result of the presence of common molecules in complex antigens of related species. In complex antigens, such as preparations of microbes, cross-reactivity may result from the presence of a variety of molecules in the preparation some of which are shared. The binding site for superantigens, unlike a processed antigen fragment, is outside the antigen-binding site of the MHC. Superantigens are a group of molecules that function very differently from traditional immunogens. An antigenic determinant is defined as a region of an antigenic molecule that fits into the combining site of an antibody. It comprises only a small part of the invading pathogen or molecuLe to which the immune system of the host has responded.
Serodiagnosis: Antibody and Antigen Detection
Johan A. Maertens, Kieren A. Marr in Diagnosis of Fungal Infections, 2007
Antibody detection tests have proved more useful in the diagnosis of endemic fungal infections, such as histoplasmosis and coccidioidomycosis, which are sometimes difficult to diagnose by traditional methods such as culture. Monoclonal antibody-based antigen detection tests offer several advantages over polyclonal antibody-based procedures, including reduced batch-to-batch variability, and the ability to generate standardized reagents in almost unlimited quantities. However, monoclonal antibody-based antigen detection tests are sometimes less sensitive than otherwise identical methods that use polyclonal antibodies. Although substantial progress has been made in improving antibody detection tests for the diagnosis of invasive candidiasis, there is a general belief that these methods are both insensitive and nonspecific. Antigen detection tests that use polyclonal antibodies raised against unpurified or semipurified fungal antigens have significant cross-reactions with other pathogenic fungi. The choice of test procedure and reagents for Aspergillus antigen detection is important.
Introduction to the Hla Antigen System
William E. Braun in HLA and Disease: A Comprehensive Review, 2019
In 1958, J. Dausset’s discovery of an antibody detecting a human leukocyte antigen (Mac) (HLA-A2) introduced the science of human histocompatibility testing. Leukocyte antigens, initially tested only for organ transplantations and later blood transfusions, are known to have a strong relationship to immune responsiveness and disease susceptibility. Population studies done throughout the world were the subject of the fifth workshop in Evian, France conducted by Dr. Dausset in 1972. It showed the strong influence of race on the frequency of histocompatibility antigens. Following the 1977 workshop, the World Health Organization HLA Nomenclature Committee provided new terminology for all of the 59 SD antigens of the A, B, and C series, the 11 LD antigens of the newly described D series, and the 7 new DR antigens. The region or system designation for the histocompatibility antigens remains HLA, formerly written HL-A.
PSCA and MUC1 in non-small-cell lung cancer as targets of chimeric antigen receptor T cells
Published in OncoImmunology, 2017
Xinru Wei, Yunxin Lai, Jin Li, Le Qin, Youdi Xu, Ruocong Zhao, Baiheng Li, Simiao Lin, Suna Wang, Qiting Wu, Qiubin Liang, Muyun Peng, Fenglei Yu, Yangqiu Li, Xuchao Zhang, Yilong Wu, Pentao Liu, Duanqing Pei, Yao Yao, Peng Li
In recent years, immunotherapies, such as those involving chimeric antigen receptor (CAR) T cells, have become increasingly promising approaches to non-small-cell lung cancer (NSCLC) treatment. In this study, we explored the antitumor potential of prostate stem cell antigen (PSCA)-redirected CAR T and mucin 1 (MUC1)-redirected CAR T cells in tumor models of NSCLC. First, we generated patient-derived xenograft (PDX) mouse models of human NSCLC that maintained the antigenic profiles of primary tumors. Next, we demonstrated the expression of PSCA and MUC1 in NSCLC, followed by the generation and confirmation of the specificity and efficacy of PSCA- and MUC1-targeting CAR T cells against NSCLC cell lines in vitro. Finally, we demonstrated that PSCA-targeting CAR T cells could efficiently suppress NSCLC tumor growth in PDX mice and synergistically eliminate PSCA+MUC1+ tumors when combined with MUC1-targeting CAR T cells. Taken together, our studies demonstrate that PSCA and MUC1 are both promising CAR T cell targets in NSCLC and that the combinatorial targeting of these antigens could further enhance the antitumor efficacy of CAR T cells.
Proteogenomics: advances in cancer antigen research
Published in Immunological Medicine, 2019
Takayuki Kanaseki, Toshihiko Torigoe
T cells recognize antigen peptides displayed by HLA molecules and specifically eliminate their target cells. Identification of responsible antigens as well as understanding the mechanism by which antigens are produced inside cells are equally crucial for cancer immunology. In this review, we introduce proteogenomics and its applications in cancer antigen research, which leverages mass spectrometry and next-generation sequencing. The approach comprehensively captures immunopeptidome displayed by HLA, revealing new classes of antigens, such as mutation-derived neoantigens, spliced peptides, and non-coding region derived peptides. These antigens may serve as therapeutic targets or biomarkers. Thus, proteogenomics is a promising approach for cancer antigen research and contributes to immunotherapy development.
EDiP: the Epitope Dilution Phenomenon. Lessons learnt from a malaria vaccine antigen and its applicability to polymorphic antigens
Published in Expert Review of Vaccines, 2018
Kwadwo Asamoah Kusi, Bart W. Faber, Gerrit Koopman, Edmond Joseph Remarque
Introduction: Polymorphism in vaccine antigens poses major challenges to vaccinologists. The Plasmodium falciparum Apical Membrane Antigen 1 (AMA1) poses such a challenge. We found that immunization with a mixture of three variants yielded functional antibody levels to all variants comparable to levels induced by monovalent immunization. The mechanism behind the observed broadening was shown to be an increase in the fraction of cross-reactive antibodies, most likely because strain-specific epitopes are present at lower frequency relative to conserved epitopes. Areas covered: We hereby introduce the Epitope Dilution Phenomenon (EDiP) as a practical strategy for the induction of broad, cross-variant antibody responses against polymorphic antigens and discuss the utility and applicability of this phenomenon for the development of vaccines against polymorphic antigens of pathogens like Influenza, HIV, Dengue and Plasmodium. Expert commentary: EDiP can be used to broaden antibody responses by immunizing with a mixture of at least 3 antigenic variants, where the variants included can differ, yet yield broadened responses.
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