Evolution of the T-Cell Receptor (TR) Loci in the Adaptive Immune Response: The Tale of the TRG Locus in Mammals

T lymphocytes are the principal actors of vertebrates’ cell-mediated immunity. Like B cells, they can recognize an unlimited number of foreign molecules through their antigen-specific heterodimer receptors (TRs), which consist of αβ or γδ chains. The diversity of the TRs is mainly due to the unique organization of the genes encoding the α, β, γ, and δ chains. For each chain, multi-gene families are arranged in a TR locus, and their expression is guaranteed by the somatic recombination process. A great plasticity of the gene organization within the TR loci exists among species. Marked structural differences affect the TR γ (TRG) locus. The recent sequencing of multiple whole genome provides an opportunity to examine the TR gene repertoire in a systematic and consistent fashion. In this review, we report the most recent findings on the genomic organization of TRG loci in mammalian species in order to show differences and similarities. The comparison revealed remarkable diversification of both the genomic organization and gene repertoire across species, but also unexpected evolutionary conservation, which highlights the important role of the T cells in the immune response.

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The immunologic V-gene repertoire in mammals

10.1101/002667 ◽

2014 ◽

Cited By ~ 2

Author(s):

David N Olivieri ◽

Bernardo von Haeften ◽

Christian Sánchez-Espinel ◽

Francisco Gambón-Deza

Keyword(s):

Mammalian Species ◽

Cell Receptor ◽

Gene Repertoire ◽

The Public ◽

Phylogenetic Studies ◽

Kappa Chain ◽

Show Evidence ◽

V Genes ◽

V Gene ◽

Additional Locus

From recent whole genome shotgun data of 48 mammalian species, we have used our software VgenExtractor to obtain the functional V-gene sequence repertoire in order to conduct comparative phylogenetic studies. These studies reveal a large variation in the number of V-genes across mammalian species, ranging from a mere 36 V-genes in dolphins to nearly 600 V-genes in rats. Monotremes and marsupials are the only mammals possessing an additional locus, the TRMV, apart from the seven common loci found in mammals. Also, we show evidence for the loss of the light chain loci, specifically the V-kappa chain in one microbat, and the V-lambda chain in one rodent species. Finally, we suggest different features related to the evolution of immunoglobulin and T cell receptor loci, where frequent sequence duplications are seen in the former, while preserved and undiversified lineages are observed in the latter. All the V-gene sequences described in this study are available in the public database repository vgenerepertoire.org.

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Neocortex expansion is linked to size variations in gene families with chemotaxis, cell–cell signalling and immune response functions in mammals

Open Biology ◽

10.1098/rsob.160132 ◽

2016 ◽

Vol 6 (10) ◽

pp. 160132

Author(s):

Atahualpa Castillo-Morales ◽

Jimena Monzón-Sandoval ◽

Alexandra A. de Sousa ◽

Araxi O. Urrutia ◽

Humberto Gutierrez

Keyword(s):

Immune Response ◽

Adult Development ◽

Brain Size ◽

Mammalian Species ◽

Cell Signalling ◽

Relative Size ◽

Brain Evolution ◽

Gene Families ◽

Evolutionary Innovation ◽

Cell Cell

Increased brain size is thought to have played an important role in the evolution of mammals and is a highly variable trait across lineages. Variations in brain size are closely linked to corresponding variations in the size of the neocortex, a distinct mammalian evolutionary innovation. The genomic features that explain and/or accompany variations in the relative size of the neocortex remain unknown. By comparing the genomes of 28 mammalian species, we show that neocortical expansion relative to the rest of the brain is associated with variations in gene family size (GFS) of gene families that are significantly enriched in biological functions associated with chemotaxis, cell–cell signalling and immune response. Importantly, we find that previously reported GFS variations associated with increased brain size are largely accounted for by the stronger link between neocortex expansion and variations in the size of gene families. Moreover, genes within these families are more prominently expressed in the human neocortex during early compared with adult development. These results suggest that changes in GFS underlie morphological adaptations during brain evolution in mammalian lineages.

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The genome of the plague-resistant great gerbil reveals species-specific duplication of an MHCII gene

10.1101/449553 ◽

2018 ◽

Cited By ~ 2

Author(s):

Pernille Nilsson ◽

Monica H. Solbakken ◽

Boris V. Schmid ◽

Russell J. S. Orr ◽

Ruichen Lv ◽

...

Keyword(s):

Adaptive Immune Response ◽

Gene Families ◽

Comparative Genomic ◽

Immune Gene ◽

Gene Repertoire ◽

Great Gerbil ◽

Genomic Landscape ◽

A Genome ◽

Natural Hosts ◽

Species Specific

AbstractThe great gerbil (Rhombomys opimus) is a social rodent living in permanent, complex burrow systems distributed throughout Central Asia, where it serves as the main host of several important vector-borne infectious diseases and is defined as a key reservoir species for plague (Yersinia pestis). Studies from the wild have shown that the great gerbil is largely resistant to plague but the genetic basis for resistance is yet to be determined. Here, we present a highly contiguous annotated genome assembly of great gerbil, covering over 96 % of the estimated 2.47 Gb genome. Comparative genomic analyses focusing on the immune gene repertoire, reveal shared gene losses within TLR gene families (i.e. TLR8, TLR10 and all members of TLR11-subfamily) for the Gerbillinae lineage, accompanied with signs of diversifying selection of TLR7 and TLR9. Most notably, we find a great gerbil-specific duplication of the MHCII DRB locus. In silico analyses suggest that the duplicated gene provides high peptide binding affinity for Yersiniae epitopes. The great gerbil genome provides new insights into the genomic landscape that confers immunological resistance towards plague. The high affinity for Yersinia epitopes could be key in our understanding of the high resistance in great gerbils, putatively conferring a faster initiation of the adaptive immune response leading to survival of the infection. Our study demonstrates the power of studying zoonosis in natural hosts through the generation of a genome resource for further comparative and experimental work on plague survival and evolution of host-pathogen interactions.

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Human Dendritic Cells Are Activated by Dengue Virus Infection: Enhancement by Gamma Interferon and Implications for Disease Pathogenesis

Journal of Virology ◽

10.1128/jvi.75.8.3501-3508.2001 ◽

2001 ◽

Vol 75 (8) ◽

pp. 3501-3508 ◽

Cited By ~ 159

Author(s):

Daniel H. Libraty ◽

Sathit Pichyangkul ◽

Chuanpis Ajariyakhajorn ◽

Timothy P. Endy ◽

Francis A. Ennis

Keyword(s):

Immune Response ◽

Dendritic Cells ◽

Virus Infection ◽

Dengue Virus ◽

Adaptive Immune Response ◽

Interleukin 12 ◽

Cell Mediated Immunity ◽

Dengue Virus Infection ◽

Adaptive Immune ◽

Ifn Γ

ABSTRACT The ability of dendritic cells (DCs) to shape the adaptive immune response to viral infection is mediated largely by their maturation and activation state as determined by the surface expression of HLA molecules, costimulatory molecules, and cytokine production. Dengue is an emerging arboviral disease where the severity of illness is influenced by the adaptive immune response to the virus. In this report, we have demonstrated that dengue virus infects and replicates in immature human myeloid DCs. Exposure to live dengue virus led to maturation and activation of both the infected and surrounding, uninfected DCs and stimulated production of tumor necrosis factor alpha (TNF-α) and alpha interferon (IFN-α). Activation of the dengue virus-infected DCs was blunted compared to the surrounding, uninfected DCs, and dengue virus infection induced low-level release of interleukin-12 p70 (IL-12 p70), a key cytokine in the development of cell-mediated immunity (CMI). Upon the addition of IFN-γ, there was enhanced activation of dengue virus-infected DCs and enhanced dengue virus-induced IL-12 p70 release. The data suggest a model whereby DCs are the early, primary target of dengue virus in natural infection and the vigor of CMI is modulated by the relative presence or absence of IFN-γ in the microenvironment surrounding the virus-infected DCs. These findings are relevant to understanding the pathogenesis of dengue hemorrhagic fever and the design of new vaccination and therapeutic strategies.

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Immunogenicity Measures of Influenza Vaccines: A Study of 1164 Registered Clinical Trials

Vaccines ◽

10.3390/vaccines8020325 ◽

2020 ◽

Vol 8 (2) ◽

pp. 325 ◽

Cited By ~ 1

Author(s):

Alexander Domnich ◽

Ilaria Manini ◽

Donatella Panatto ◽

Giovanna Elisa Calabrò ◽

Emanuele Montomoli

Keyword(s):

Immune Response ◽

Influenza Vaccine ◽

Humoral Immune Response ◽

Adaptive Immune Response ◽

Point Of View ◽

Influenza Vaccines ◽

Study Phase ◽

Cell Mediated Immunity ◽

Humoral Immune ◽

Immunological Assays

Influenza carries an enormous burden each year. Annual influenza vaccination is the best means of reducing this burden. To be clinically effective, influenza vaccines must be immunogenic, and several immunological assays to test their immunogenicity have been developed. This study aimed to describe the patterns of use of the various immunological assays available to measure the influenza vaccine-induced adaptive immune response and to determine its correlates of protection. A total of 76.5% of the studies included in our analysis measured only the humoral immune response. Among these, the hemagglutination-inhibition assay was by far the most widely used. Other, less common, humoral immune response assays were: virus neutralization (21.7%), enzyme-linked immunosorbent (10.1%), single radial hemolysis (4.6%), and assays able to quantify anti-neuraminidase antibodies (1.7%). By contrast, cell-mediated immunity was quantified in only 23.5% of studies. Several variables were significantly associated with the use of single assays. Specifically, some influenza vaccine types (e.g., adjuvanted, live attenuated and cell culture-derived or recombinant), study phase and study sponsorship pattern were usually found to be statistically significant predictors. We discuss the principal findings and make some suggestions from the point of view of the various stakeholders.

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Host-Adapted Gene Families Involved in Murine Cytomegalovirus Immune Evasion

Viruses ◽

10.3390/v14010128 ◽

2022 ◽

Vol 14 (1) ◽

pp. 128

Author(s):

Sara Becker ◽

Annette Fink ◽

Jürgen Podlech ◽

Matthias J. Reddehase ◽

Niels A. Lemmermann

Keyword(s):

Immune Response ◽

Immune Evasion ◽

Clinical Investigation ◽

Viral Evolution ◽

Adaptive Immune Response ◽

Gene Families ◽

Murine Cytomegalovirus ◽

Adaptive Immune ◽

Species Specific

Cytomegaloviruses (CMVs) are host species-specific and have adapted to their respective mammalian hosts during co-evolution. Host-adaptation is reflected by “private genes” that have specialized in mediating virus-host interplay and have no sequence homologs in other CMV species, although biological convergence has led to analogous protein functions. They are mostly organized in gene families evolved by gene duplications and subsequent mutations. The host immune response to infection, both the innate and the adaptive immune response, is a driver of viral evolution, resulting in the acquisition of viral immune evasion proteins encoded by private gene families. As the analysis of the medically relevant human cytomegalovirus by clinical investigation in the infected human host cannot make use of designed virus and host mutagenesis, the mouse model based on murine cytomegalovirus (mCMV) has become a versatile animal model to study basic principles of in vivo virus-host interplay. Focusing on the immune evasion of the adaptive immune response by CD8+ T cells, we review here what is known about proteins of two private gene families of mCMV, the m02 and the m145 families, specifically the role of m04, m06, and m152 in viral antigen presentation during acute and latent infection.

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The Presence of Alpha Interferon at the Time of Infection Alters the Innate and Adaptive Immune Responses to Porcine Reproductive and Respiratory Syndrome Virus

Clinical and Vaccine Immunology ◽

10.1128/cvi.05490-11 ◽

2012 ◽

Vol 19 (4) ◽

pp. 508-514 ◽

Cited By ~ 23

Author(s):

Susan L. Brockmeier ◽

Crystal L. Loving ◽

Eric A. Nelson ◽

Laura C. Miller ◽

Tracy L. Nicholson ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Adaptive Immune Response ◽

Alpha Interferon ◽

Respiratory Syndrome Virus ◽

Cell Mediated Immunity ◽

Swine Industry ◽

Adaptive Immune Responses ◽

Adaptive Immune ◽

Time Of Infection

ABSTRACTPorcine reproductive and respiratory syndrome (PRRS) is one of the most devastating and costly diseases to the swine industry worldwide. Overall, the adaptive immune response to PRRS virus (PRRSV) is weak, which results in delayed elimination of virus from the host and inferior vaccine protection. PRRSV has been shown to induce a meager alpha interferon (IFN-α) response, and we hypothesized that elevated IFN-α levels early in infection would shorten the induction time and increase elements of the adaptive immune response. To test this, we measured both antibody and cell-mediated immunity in pigs after the administration of a nonreplicating human adenovirus type 5 vector expressing porcine IFN-α (Ad5–pIFN-α) at the time of PRRSV infection and compared the results to those for pigs infected with PRRSV alone. Viremia was delayed, and there was a decrease in viral load in the sera of pigs administered the Ad5–pIFN-α. Although seroconversion was slightly delayed in pigs receiving Ad5–pIFN-α, probably due to the early reduction in viral replication, little difference in the overall or neutralizing antibody response was seen. However, there was an increase in the number of virus-specific IFN-γ-secreting cells detected in the pigs receiving Ad5–pIFN-α, as well as an altered cytokine profile in the lung at 14 days postinfection, indicating that the presence of IFN-α at the time of infection can alter innate and adaptive immune responses to PRRSV.

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Hatching time for monotreme immunology

Australian Journal of Zoology ◽

10.1071/zo09042 ◽

2009 ◽

Vol 57 (4) ◽

pp. 185 ◽

Cited By ~ 9

Author(s):

Emily S. W. Wong ◽

Anthony T. Papenfuss ◽

Robert D. Miller ◽

Katherine Belov

Keyword(s):

T Cell ◽

Gene Families ◽

Cell Receptor ◽

Immune Gene ◽

Gene Repertoire ◽

Anatomy And Physiology ◽

Hatching Time ◽

Platypus Genome ◽

History Of ◽

Health And Disease

The sequencing of the platypus genome has spurred investigations into the characterisation of the monotreme immune response. As the most divergent of extant mammals, the characterisation of the monotreme immune repertoire allows us to trace the evolutionary history of immunity in mammals and provide insights into the immune gene complement of ancestral mammals. The immune system of monotremes has remained largely uncharacterised due to the lack of specific immunological reagents and limited access to animals for experimentation. Early immunological studies focussed on the anatomy and physiology of the lymphoid system in the platypus. More recent molecular studies have focussed on characterisation of individual immunoglobulin, T-cell receptor and MHC genes in both the platypus and short-beaked echidna. Here, we review the published literature on the monotreme immune gene repertoire and provide new data generated from genome analysis on cytokines, Fc receptors and immunoglobulins. We present an overview of key gene families responsible for innate and adaptive immunity including the cathelicidins, defensins, T-cell receptors and the major histocompatibility complex (MHC) Class I and Class II antigens. We comment on the usefulness of these sequences for future studies into immunity, health and disease in monotremes.

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