Immunoglobulin Superfamily Virus Receptors and the Evolution of Adaptive Immunity

Dermody, Terence S.; Kirchner, Eva; Guglielmi, Kristen M.; Stehle, Thilo

doi:10.1371/journal.ppat.1000481

Cited by 51 publications

(52 citation statements)

References 47 publications

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“…Nevertheless, assuming protection from infection as the primary driver of receptor selection, viral or bacterial receptor molecules encoding either a V or closely related intermediate (I)-type domain would be attractive candidates for the earliest receptors70. Although molecules such as viral receptors can be viewed as pathogen adaptation to a host cell, they could function in protection if they were adapted to a secretory function that could block viral attachment to the cell70. Any number of other related molecular types could also have been an effective antigen-binding receptor precursor into which a rearrangement mechanism was introduced.…”

Section: Earliest Conventional Adaptive Immune Receptormentioning

confidence: 99%

The origins of vertebrate adaptive immunity

2010

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Adaptive immunity is mediated through numerous genetic and cellular processes that generate favourable somatic variants of antigen-binding receptors under evolutionary selection pressure by pathogens and other factors. Advances in our understanding of immunity in mammals and other model organisms are revealing the underlying basis and complexity of this remarkable system. Although the evolution of adaptive immunity has been considered to occur by acquisition of novel molecular capabilities, an increasing amount of information from new model systems suggest that co-option and redirection of preexisting systems are the major source of innovation. We combine evidence from a wide range of organisms to obtain an integrated view of the origins and patterns of divergence in adaptive immunity.With our increased understanding of mammalian adaptive immunity over the past decade, we have come to recognize the remarkable complexity of its underlying mechanisms. The core elements of this system are now mechanistically understood, such as DNA rearrangement, the generation of immune recognition diversity and the supporting cellular complexity that selects and expands cell populations expressing favourable antigen-binding receptor variants. General features of mammalian adaptive immunity -such as clonal selection, compartmental differentiation of lymphocytes, somatic hypermutation (SHM), allelic exclusion and a form of immunological memory -appeared before the emergence of the modern jawed vertebrates. Over the past several years, studies of immune receptors and immunity in a wide range of vertebrate and invertebrate species have revealed several similarities to present-day mammalian immunity and have provided insights into the evolutionary acquisition of immunological complexity 1,2 . We are within reach of important breakthroughs in our understanding of how adaptive immunity evolved in the context of an innate immune system and how these molecularly disparate systems are related and remain interdependent 3 . What has become increasingly clear is that the evolution of adaptive immunity requires the study of NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript a large range of molecular systems and that it cannot be understood from studies that are restricted to mice and humans or even from studies that use alternative vertebrate models, such as bony fish and sharks. Furthermore, we recognize that the complex set of processes that constitutes adaptive immunity can be addressed most effectively by examining its constituent steps; these include (not necessarily in order of evolutionary emergence or of equivalent complexity) the appearance of lymphocytes, the acquisition of antigen-binding receptor diversification mechanisms, the structural basis for recognition specificity, the evolution of mechanisms for receptor selection and the regulatory processes that target and attenuate immune responses. We are now in a better position to understand these essential steps in the evolutionary acquisition of ada...

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Section: Earliest Conventional Adaptive Immune Receptormentioning

confidence: 99%

The origins of vertebrate adaptive immunity

2010

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“…The secreted forms of CD155 are detectable in cultured cell medium, human serum, and human cerebrospinal fluid, and have the capacity to limit viral entry by blocking binding to membrane-bound CD155 (Baury et al, 2003). In fact, many viral receptors are members of the immunoglobulin superfamily, and since most viruses bind these proteins at the most membrane-distal site, it has been suggested that soluble forms of viral receptors may be precursors to modern antibodies, and that soluble receptors neutralize viruses by competing with receptors on the cell surface (Dermody et al, 2009). While this idea of soluble receptor-mediated poliovirus neutralization has not been examined in vivo and may be operative during human infections, current transgenic mouse models express only the membrane-bound form of CD155, therefore, soluble CD155 is unlikely to contribute to the major host barriers observed in this mouse model (see below)(Koike et al, 1990; Koike et al, 1991; Kuss, Etheredge, and Pfeiffer, 2008; Lancaster and Pfeiffer, 2010; Ren et al, 1990).…”

Section: Poliovirus Route and Barriersmentioning

confidence: 99%

Innate Host Barriers to Viral Trafficking and Population Diversity

Pfeiffer

2010

Advances in Virus Research

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Poliovirus is an error-prone enteric virus spread by the fecal-oral route, and rarely invades the central nervous system (CNS). However, in the rare instances when poliovirus invades the CNS, the resulting damage to motor neurons is striking and often permanent. In the pre-vaccine era, it is likely that most individuals within an epidemic community were infected; however, only 0.5% of infected individuals developed paralytic poliomyelitis. Paralytic poliomyelitis terrified the public and initiated a huge research effort, which was rewarded with two outstanding vaccines. During research to develop the vaccines, many questions were asked: Why did certain people develop paralysis? How does the virus move from the gut to the CNS? What limits viral trafficking to the CNS in the vast majority of infected individuals? Despite over 100 years of poliovirus research, many of these questions remain unanswered. The goal of this chapter is to review our knowledge of how poliovirus moves within and between hosts, how host barriers limit viral movement, how viral population dynamics impact viral fitness and virulence, and to offer hypotheses to explain the rare incidence of paralytic poliovirus disease.

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“…The two sides of the sandwich motif is covalently linked by disulfide bonds. Variable forms of the immunoglobulin fold have been widely identified in immune modulators, and viral receptors [50,51,52,53]. …”

Section: Structure Of Immunoglobulinmentioning

confidence: 99%

Structure Based Antibody-Like Peptidomimetics

Murali

Greene

2012

Pharmaceuticals

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Biologics such as monoclonal antibodies (mAb) and soluble receptors represent new classes of therapeutic agents for treatment of several diseases. High affinity and high specificity biologics can be utilized for variety of clinical purposes. Monoclonal antibodies have been used as diagnostic agents when coupled with radionuclide, immune modulatory agents or in the treatment of cancers. Among other limitations of using large molecules for therapy the actual cost of biologics has become an issue. There is an effort among chemists and biologists to reduce the size of biologics which includes monoclonal antibodies and receptors without a reduction of biological efficacy. Single chain antibody, camel antibodies, Fv fragments are examples of this type of deconstructive process. Small high-affinity peptides have been identified using phage screening. Our laboratory used a structure-based approach to develop small-size peptidomimetics from the three-dimensional structure of proteins with immunoglobulin folds as exemplified by CD4 and antibodies. Peptides derived either from the receptor or their cognate ligand mimics the functions of the parental macromolecule. These constrained peptides not only provide a platform for developing small molecule drugs, but also provide insight into the atomic features of protein-protein interactions. A general overview of the reduction of monoclonal antibodies to small exocyclic peptide and its prospects as a useful diagnostic and as a drug in the treatment of cancer are discussed.

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Immunoglobulin Superfamily Virus Receptors and the Evolution of Adaptive Immunity

Cited by 51 publications

References 47 publications

The origins of vertebrate adaptive immunity

The origins of vertebrate adaptive immunity

Innate Host Barriers to Viral Trafficking and Population Diversity

Structure Based Antibody-Like Peptidomimetics

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