This short review discusses the evolution of the immunoglobulins and the development of the diversity of antibodies. Birds and mammals represent two lines of development having divided more than 300 million years ago. In the immunoglobulins and antibody-systems there are many similarities which, however, are based on analogies. In this sense the dominant humoral type of immunoglobulin is IgY in birds and opposed to IgG in the mammals. Also, the mechanisms differ which lead to the diversity of antibodies. In mammals predominantly recombination of gen-segments and somatic mutations lead to this diversity, in birds gen-conversion shows a greater significance. In this way comparable results are produced through different structures or mechanisms.
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Proc Natl Acad Sci U S A
February 2025
U.S. Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910.
HIV-1 envelope broadly neutralizing antibodies represent a promising component of HIV-1 cure strategies. To evaluate the therapeutic efficacy of combination monoclonal antibodies (mAbs) in a rigorous nonhuman primate model, we tested different combinations of simian immunodeficiency virus (SIV) neutralizing mAbs in SIVmac251-infected rhesus macaques. Antiretroviral therapy-suppressed animals received anti-SIV mAbs targeting multiple Env epitopes spanning analytical treatment interruption (ATI) in 3 groups (n = 7 each): i) no mAb; ii) 4-mAb combination; and iii) 2-mAb combination.
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November 2024
Department of Computer Science, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon Tong, Hong Kong, 999077, China.
The complexity of T cell receptor (TCR) sequences, particularly within the complementarity-determining region 3 (CDR3), requires efficient embedding methods for applying machine learning to immunology. While various TCR CDR3 embedding strategies have been proposed, the absence of their systematic evaluations created perplexity in the community. Here, we extracted CDR3 embedding models from 19 existing methods and benchmarked these models with four curated datasets by accessing their impact on the performance of TCR downstream tasks, including TCR-epitope binding affinity prediction, epitope-specific TCR identification, TCR clustering, and visualization analysis.
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January 2025
Guangdong Provincial Key Laboratory of Digestive Cancer Research, Digestive Diseases Center, Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong 518107, P.R. China.
CRISPR-Cas12a technology has transformative potential, but as its applications grow, enhancing its inherent functionalities is essential to meet diverse demands. Here, we reveal a regulatory mechanism for LbCas12a through direct repeat (DR) region 3' end modifications and de-modifications, which can regulate LbCas12a's cis- and trans-cleavage activities. We extensively explored the effects of introducing phosphorylation, DNA, photo-cleavable linker, DNA modifications at the DR 3' end on LbCas12a's functionality.
View Article and Find Full Text PDFColorectal cancer (CRC) is the second leading cause of cancer-related mortality globally. While immunotherapeutic approaches are effective in a subset of CRC patients, the majority of CRC cases receive limited benefits from immunotherapy. This study developed an immune subtype classification system based on diverse immune cells and pathways.
View Article and Find Full Text PDFCommun Biol
January 2025
Large Molecules Research, Sanofi, Cambridge, MA, USA.
Antibodies, essential components of adaptive immunity, derive their remarkable diversity primarily from V(D)J gene rearrangements, particularly within the heavy chain complementarity-determining region 3 (CDR-H3) where D genes play a major role. Traditionally, D genes were thought to recombine only in the forward direction, despite having identical recombination signal sequences (12 base pair spacers) at both ends. This observation led us to question whether these symmetrical sequences might enable bidirectional recombination.
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