Salp15, an Ixodes scapularis Salivary Protein, Inhibits CD4+ T Cell Activation

Anguíta, Juan; Ramamoorthi, Nandhini; Hovius, Joppe W.; Das, Subrata; Thomas, Venetta; Persinski, Rafal; Conze, Dietrich B.; Askenase, Philip W.; Rincón, Mercedes; Kantor, Fred S.; Fikrig, Erol

doi:10.1016/s1074-7613(02)00325-4

Cited by 239 publications

(286 citation statements)

References 47 publications

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“…The C-terminal portion of Salp15 (amino acids 95-114 of the mature protein named P11, with the sequence GPNGQTCAEKNKCVGHIPGC - [17]) mediates its interaction with sCD4 [18] and recapitulates the immunosuppressive activity of Salp15 [26]. We thus tested the ability of purified P11 to compete CD4-gp120 binding.…”

Section: Resultsmentioning

confidence: 99%

“…His-tagged Salp15 and Salp15ΔP11 were purified using the Drosophila expression system (DES), as described [17]. Recombinant HIV-1 IIIB HRP-conjugated gp120 and sCD4 (domains D1D2) were purchased from Immunodiagnostics, Inc. (Woburn, MA).…”

Section: Recombinant Proteins and Synthetic Peptidesmentioning

confidence: 99%

“…Ixodes scapularis salivary protein (Salp) 15 is an antigen that mediates at least partially the immunomodulatory action of tick saliva on host-acquired immune responses [17]. Inhibition mediated by Salp15 results from the repression of calcium fluxes triggered by T cell antigen receptor (TCR) ligation and a subsequent reduction in interleukin (IL)-2 production.…”

Section: Introductionmentioning

confidence: 99%

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The Ixodes scapularis salivary protein, salp15, prevents the association of HIV-1 gp120 and CD4

Juncadella¹,

Garg²,

Bates³

et al. 2008

Biochemical and Biophysical Research Communications

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Ixodes scapularis salivary protein, Salp15, inhibits CD4 + T cell activation by binding to the mostextracellular domains of the CD4 molecule, potentially overlapping with the gp120-binding region. We now show that Salp15 inhibits the interaction of gp120 and CD4. Furthermore, Salp15 prevents syncytia formation between HL2/3 (a stable HeLa cell line expressing the envelope protein) and CD4-expressing cells. Salp15 prevented gp120-CD4 interaction at least partially through its direct interaction with the envelope glycoprotein. A phage display library screen provided the interacting residues in the C1 domain of gp120. These results provide a potential basis to define exposed gp120 epitopes for the generation of neutralizing vaccines.

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Section: Resultsmentioning

confidence: 99%

Section: Recombinant Proteins and Synthetic Peptidesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Ixodes scapularis salivary protein, salp15, prevents the association of HIV-1 gp120 and CD4

Juncadella¹,

Garg²,

Bates³

et al. 2008

Biochemical and Biophysical Research Communications

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“…A recent genetic study showed that the midgut protein TROSPA is a receptor for OspA binding, whose presence enhances colonization by B. burgdorferi [170]. The salivary gland protein Salp15 is immunosuppressive and may facilitate infection by the low numbers of spirochetes that are transmitted during tick feeding [171,172]. Recently, a tick antioxidant was shown to facilitate tick acquisition of spirochetes from infected animals [173].…”

Section: B Burgdorferi Infection Of Ticksmentioning

confidence: 99%

Biology of Infection with Borrelia burgdorferi

Tilly

Rosa

Stewart

2008

Infectious Disease Clinics of North America

183

177

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The spirochete Borrelia burgdorferi is a tick-borne obligate parasite whose normal reservoir is a variety of small mammals [1]. Whereas infection of these natural hosts does not lead to disease, infection of humans can result in Lyme disease, as a consequence of the human immunopathological response to B. burgdorferi [2,3]. Consistent with the pathogenesis of Lyme disease, bacterial products that allow B. burgdorferi to replicate and survive, rather than true "virulence factors," appear to be primarily what is required for the bacterium to cause disease in a susceptible host. In support of this idea, the genome sequence of B31, the type strain of B. burgdorferi sensu stricto [4,5], revealed that the bacterium lacks factors common to many bacterial pathogens, such as lipopolysaccharide, toxins, and specialized secretion systems. In this chapter, we will describe the basic biology of B. burgdorferi, and some of the bacterial components required to infect and survive in the mammalian and tick hosts.

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“…We have recently cloned and characterized an immunomodulatory protein present in Ixodes scapularis saliva, Salp15, which is the first I. scapularis protein known to be associated with the immunosuppressive activity of tick saliva (1). Salp15 has been shown to impair proliferative responses of anti-CD3-plus anti-CD28-activated CD4 ϩ T cells by inhibition of T-cellreceptor-mediated calcium mobilization (1).…”

mentioning

confidence: 99%