Biomedical subjects

S K Wikel

Publications and source records attributed to S K Wikel.

At least 19 recordsLinked to original sources

PubMed2005

Cellular infiltration at skin lesions and draining lymph nodes of sheep infested with adult Hyalomma anatolicum anatolicum ticks.

Immunohistochemical analysis of skin and draining lymph nodes of sheep repeatedly infested with the ixodid tick Hyalomma anatolicum anatolicum were studied for different antigen-presenting cells and lymphocyte subpopulations. Infiltration of neutrophils, macrophages and lymphocytes adjacent to the tick bite site were observed. Skin biopsies showed significant increases in dermal infiltration of CD8+ and gammadelta+ T cells at 72 h and 8 days after both primary and secondary infestation. Infiltrations of MHC-II DR/DQ decreased at 72 h after tick infestation, whereas significant increases were recorded for 8-day skin biopsies. CD1+ cellular infiltrations were observed during secondary infestations at the dermis. Decreased ratios of CD4:CD8 T cells and MHC-II:CD1 antigen-presenting cells were observed in both infestations compared to healthy skin biopsies. Ratios of alphabeta:gammadelta T cells increased gradually during infestation compared to uninfested skin. The regional lymph nodes from tick-infested sheep showed an increased CD8+, gammadelta+ T and CD1+ cellular infiltration compared to control lymph nodes. CD4+ T cells were decreased. There were no significant changes in CD45R+ cellular infiltration either at skin lesions or regional lymph nodes.

Animals↗

PubMed2005

Murine extramedullary erythropoiesis induced by tick infestation.

Tick saliva contains molecules that modulate the haemostasis, pain/itch responses, wound healing and immune defences of the host. Using BALB/c mice that were each infested with 10 nymphs of Dermacentor andersoni Stiles (Acari: Ixodidae), an attempt has now been made to determine the influence of tick infestation on the expression of leucocyte adhesion molecules in the host. The ticks became fully engorged by the fourth to sixth day of infestation. On the fourth day of infestation, the results of flow cytometry indicated that 2% of the host's splenocytes were expressing high levels of CD49 (alpha4 integrin of VLA-4) and low levels of CD11a (alphaL subunit of the integrin LFA-1). By the eighth day of infestation, 30% of the hosts' splenocytes had this phenotype and were negative for the lineage markers CD3e (T-lymphocytes), DX5 (natural-killer cells of a BALB/c lineage), B220 (B-lymphocytes), CD11b (monocytes/macrophages, granulocytes, natural-killer cells, activated T-lymphocytes, and B-1 cells) and CD11c (myeloid and splenic dendritic cells). Histological examination of the spleens from infested mice revealed disruption of the white-pulp/red-pulp demarcations and the presence of a large number of basophilic normoblasts. The CD11a(lo) population of splenocytes from the tick-infested mice was positive for TER-119 but negative for CD3, B220, CD11b and Gr, confirming that the splenocytes were members of the erythroid lineage. These results indicate that, within 8 days of their initiation, the tick infestations induced extramedullary erythropoiesis in the spleens of their murine hosts.

Animals↗

PubMed2005

Tick modulation of the in-vitro expression of adhesion molecules by skin-derived endothelial cells.

As a tick feeds, its saliva induces innate and acquired immune responses in the host, including leucocyte infiltration into the bite site. Tick salivary glands produce molecules, however, that counteract many host defences against blood feeding. The effects of salivary-gland extracts (SGE) of Dermacentor andersoni and Ixodes scapularis on the expression of various adhesion molecules [E-selectin, P-selectin, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1)] by the sEND.1 cell line (which is based on cells from the subcutaneous tissue of mice) have now been investigated in vitro. The effects were found to differ with the tick species. The SGE of D. andersoni significantly down-regulated the expression of ICAM-1, whereas a similar extract prepared from I. scapularis significantly reduced the expression of P-selectin and VCAM-1. Tick salivary proteins therefore appear to have direct effects on adhesion-molecule expression, in addition to their previously established roles in down-regulating the pro-inflammatory cytokines that activate endothelial cells. It remains unclear exactly how the reduction of adhesion-molecule expression in the host's endothelial cells benefits the feeding tick but it may alter leucocyte migration to the bite site and/or reduce antigen presentation by the endothelial cells. It may also modulate the interactions between the host's leucocytes and any tick-borne pathogens, during initial infection of the endothelium.

Animals↗

PubMed2004

Tick immunobiology.

Ticks are of vast medical and veterinary public health importance due to direct damage caused by feeding and their roles in transmitting well known and emerging infectious agents. Ticks and tick-borne pathogens stimulate the immune system of the host. Those immune interactions are of importance in tick biology, pathogen transmission and control of ticks and tick-borne diseases. Both innate and specific acquired immune defenses are involved in the responses of vertebrate hosts to infestation. Ticks have evolved countermeasures to circumvent host immune defenses. This review addresses the immunobiology of the tick-host interface from the perspectives of the pharmacology of tick saliva; relationship of tick saliva to pathogen transmission; host immune responses to infestation; tick modulation of host immune defences; and genomic/proteomic strategies for studying tick salivary gland molecules.

Animals↗

PubMed2001

Progress toward molecular characterization of ectoparasite modulation of host immunity.

Ectoparasitic arthropods and vector-borne infectious agents are global medical and veterinary public health concerns. Economic impact due to direct effects of infestation and disease transmission are significant. These problems are increased by development of arthropod resistance to insecticides/acaricides; drug resistance of vector-borne pathogens; and, lack of effective vaccines to prevent many of these diseases. There is much to be gained from understanding the complex array of immunological interactions occurring at the arthropod-host-pathogen interface. One application of that knowledge is the development of novel vaccines for the control of both ectoparasitic arthropods and the diseases they transmit. We now realize that blood-feeding arthropods are not simply flying or crawling hypodermic needles and syringes. Ectoparasitic arthropods are not passive partners in their relationships with the immune systems of their hosts. These clever invertebrates produce numerous pharmacologically active molecules that help them migrate through tissues of their hosts or to successfully obtain blood meals. Arthropod parasites stimulate a spectrum of host immune responses that could potentially impair development, reduce feeding success, or kill the ectoparasite. Not unexpectedly, arthropods have developed sophisticated arsenals of countermeasures that modulate or deviate host immune responses. Not only does arthropod modulation of host immunity facilitate survival in tissues or increase the likelihood of obtaining a blood meal, but it is increasingly recognized as a critical factor in pathogen transmission. Those countermeasures to host immune defenses are the topics of this review. Emphasis is placed on our current understanding of the molecular bases of those changes; the molecules responsible for host immunomodulation; contemporary approaches for studying these complex relationships; and, the potential for using this information to develop innovative vaccine-based control strategies.

Animals↗

PubMed2001

Dermacentor andersoni: effects of repeated infestations on lymphocyte proliferation, cytokine production, and adhesion-molecule expression by BALB/c mice.

The effects of repeated infestations with Dermacentor andersoni nymphs on the lymphocyte functions of BALB/c mice were investigated. The in-vitro proliferation responses to concanavalin-A or salivary-gland molecules, the production of cytokines, and the expression of two adhesion molecules-leucocyte function-associated antigen-1 (LFA-1) and very late activation-4 (VLA-4)-were all studied. In addition, the ability of salivary-gland extract or saliva from D. andersoni to modulate expression of lymphocyte adhesion molecules in vitro was determined. The proliferative responses of T-lymphocytes to concanavalin-A were significantly suppressed after first and second infestations, and significant increases in lymphocyte proliferation in the presence of tick salivary-gland antigen were observed in infested mice. After two infestations, production of interleukin-2 was significantly decreased but that of interferon-gamma remained unchanged. Production of interleukin-4 and interleukin-10 was significantly enhanced in infested mice after both the first and second infestations. Expression of LFA-1 and VLA-4 by lymphocytes from infested mice was suppressed. Furthermore, both a salivary-gland extract and the saliva of D. andersoni reduced the in-vitro expression of both of these adhesion molecules by lymphocytes from tick-naive mice.

Analysis of Variance↗

PubMed2001

Modulation of host immunity by haematophagous arthropods.

The medical and veterinary public-health importance of haematophagous arthropods is immense and continuing to increase because of the emergence of new vector-borne infectious agents and the resurgence of well known ones. Control of blood-feeding arthropods and the pathogens they transmit is compounded by drug, insecticide and acaricide resistance. Novel control strategies are needed. Immunological control is one very promising approach to these problems. In order to develop anti-arthropod vaccines that block pathogen transmission and establishment, the immunological interactions occurring at the interface of the blood-feeding arthropod and host must be characterized. An important component of these interactions is arthropod modulation of the host's innate and acquired, specific immune defences. This review discusses current knowledge regarding the ability of haematophagous arthropods to alter their hosts' immune defences, the impact of those changes on pathogen transmission, the molecular bases for the immunomodulation, and strategies for identification of the molecules in arthropod saliva that are responsible for the immunomodulation.

Animals↗

PubMed2001

Regulation of OspE-related, OspF-related, and Elp lipoproteins of Borrelia burgdorferi strain 297 by mammalian host-specific signals.

In previous studies we have characterized the cp32/18 loci in Borrelia burgdorferi 297 which encode OspE and OspF orthologs and a third group of lipoproteins which possess OspE/F-like leader peptides (Elps). To further these studies, we have comprehensively analyzed their patterns of expression throughout the borrelial enzootic cycle. Serial dilution reverse transcription-PCR analysis indicated that although a shift in temperature from 23 to 37 degrees C induced transcription for all nine genes analyzed, this effect was often markedly enhanced in mammalian host-adapted organisms cultivated within dialysis membrane chambers (DMCs) implanted within the peritoneal cavities of rats. Indirect immunofluorescence assays performed on temperature-shifted, in vitro-cultivated spirochetes and organisms in the midguts of unfed and fed ticks revealed distinct expression profiles for many of the OspE-related, OspF-related, and Elp proteins. Other than BbK2.10 and ElpA1, all were expressed by temperature-shifted organisms, while only OspE, ElpB1, OspF, and BbK2.11 were expressed in the midguts of fed ticks. Additionally, although mRNA was detected for all nine lipoprotein-encoding genes, two of these proteins (BbK2.10 and ElpA1) were not expressed by spirochetes cultivated in vitro, within DMCs, or by spirochetes within tick midguts. However, the observation that B. burgdorferi-infected mice generated specific antibodies against BbK2.10 and ElpA1 indicated that these antigens are expressed only in the mammalian host and that a form of posttranscriptional regulation is involved. Analysis of the upstream regions of these genes revealed several differences between their promoter regions, the majority of which were found in the -10 and -35 hexamers and the spacer regions between them. Also, rather than undergoing simultaneous upregulation during tick feeding, these genes and the corresponding lipoproteins appear to be subject to progressive recruitment or enhancement of expression as B. burgdorferi is transmitted from its tick vector to the mammalian host. These findings underscore the potential relevance of these molecules to the pathogenic events of early Lyme disease.

Animals↗

PubMed2000

Interdependence of environmental factors influencing reciprocal patterns of gene expression in virulent Borrelia burgdorferi.

The paradigm for differential antigen expression in Borrelia burgdorferi, the agent of Lyme disease, is the reciprocal expression of its outer surface (lipo)proteins (Osp) A and C; as B. burgdorferi transitions from its arthropod vector into mammalian tissue, ospC is upregulated, and ospA is downregulated. In the current study, using B. burgdorferi cultivated under varying conditions in BSK-H medium, we found that a decrease in pH, in conjunction with increases in temperature (e.g. 34 degrees C or 37 degrees C) and cell density, acted interdependently for the reciprocal expression of ospC and ospA. The lower pH (6.8), which induced the reciprocal expression of ospC and ospA in BSK-H medium, correlated with a drop in pH from 7.4 to 6.8 of tick midgut contents during tick feeding. In addition to ospC and ospA, other genes were found to be regulated in reciprocal fashion. Such genes were either ospC-like (e.g. ospF, mlp-8 and rpoS) (group I) or ospA-like (lp6.6 and p22) (group II); changes in expression occurred at the mRNA level. That the expression of rpoS, encoding a putative stress-related alternative sigma factor (sigma(s)), was ospC-like suggested that the expression of some of the group I genes may be controlled through sigma(s). The combined results prompt a model that allows for predicting the regulation of other B. burgdorferi genes that may be involved in spirochaete transmission, virulence or mammalian host immune responses.

Animals↗

PubMed2000

Cytokine responses of C3H/HeN mice infested with Ixodes scapularis or Ixodes pacificus nymphs.

Lyme borreliosis, caused by Borrelia burgdorferi, is transmitted by Ixodes scapularis in the eastern and midwestern United States and by Ixodes pacificus in the far-Western United States. Studies have shown that infestation with I. scapularis nymphs modulates host cytokine production; however, the influence of I. pacificus infestation on host cytokines remains uninvestigated. This study demonstrated how repeated infestations with pathogen-free I. scapularis or I. pacificus nymphs affects the production of the macrophage cytokines IL-1beta, IL-6 and tumour necrosis factor-alpha and the T lymphocyte cytokines IL-2, IL-4, IL-5, IL-6, IL-10 and IFN-gamma by C3H/HeN mice. Female mice were infested once or twice with pathogen-free I. scapularis or I. pacificus nymphs, with a 14-day tick-free period between exposures. After each infestation, tick biology parameters were assessed and macrophage and T lymphocyte cytokine production measured by antigen capture ELISA. Acquired resistance to tick feeding did not develop after infestation with either tick species. Differences in cytokine production were observed between infested and noninfested mice, and between mice infested with either I. scapularis or I. pacificus nymphs. Infestations polarized cytokine production towards a Th2 cytokine profile, with suppression of pro-inflammatory Th1 cytokines. This pattern of cytokine production is more pronounced for I. pacificus infested mice.

Animals↗

PubMed2000

Influence of soluble proteins from the salivary glands of ixodid ticks on the in-vitro proliferative responses of lymphocytes from BALB/c and C3H/HeN mice.

In the U.S.A., Borrelia burgdorferi, the causative agent of Lyme borreliosis, is transmitted to humans by the ticks Ixodes scapularis and I. pacificus. Tick modulation of host immunity is an important factor in tick transmission of such pathogens. The proliferative responses of lymphocytes from BALB/c and C3H/HeN mice exposed to the salivary-gland soluble proteins (SGSP) of I. scapularis, I. pacificus or Dermacentor andersoni were therefore compared in vitro. This produced the present report, the first to describe the effects of I. pacificus SGSP on the proliferative responses of a host's lymphocytes in vitro. The effects of four concentrations of SGSP from each tick species were evaluated with unstimulated, and concanavalin-A-stimulated lymphocytes of each mouse strain. The responses of lymphocytes from both mouse strains were significantly effected when exposed to SGSP derived from each tick species. Responses of the unstimulated lymphocytes to SGSP indicated that the proteins from I. pacificus suppressed in-vitro lymphocyte proliferation to a greater degree than those from the other species investigated. For the concanavalin-A stimulated cells, however, suppression of the proliferative responses was greatest for cells exposed to I. scapularis SGSP.

Animals↗

PubMed2000

Decorin-binding protein A (DbpA) of Borrelia burgdorferi is not protective when immunized mice are challenged via tick infestation and correlates with the lack of DbpA expression by B. burgdorferi in ticks.

Previous studies showed that decorin-binding protein A (DbpA) of Borrelia burgdorferi was a protective immunogen in the murine model of Lyme borreliosis when mice were challenged (needle inoculated) intradermally with in vitro-cultivated spirochetes. In the present study, DbpA-immunized C3H/HeJ mice were not protected from infection when infested with Ixodes scapularis nymphs harboring virulent B. burgdorferi 297. This lack of protection correlated with the failure to detect DbpA on B. burgdorferi in ticks, suggesting that DbpA is not available as a target for bactericidal antibodies in serum when B. burgdorferi-infected ticks take their blood meal from an immunized host. The failure of DbpA immunization to protect tick-challenged mice contradicts the results of earlier needle inoculation vaccination experiments and suggests that DbpA may not be suitable as a Lyme disease vaccine.

Adhesins, Bacterial↗

PubMed2000

Influence of repeated infestations with pathogen-free Ixodes scapularis (Acari: Ixodidae) on in vitro lymphocyte proliferation responses of C3H/HeN mice.

In the United States, Ixodes scapularis Say has been implicated as the vector of at least three human pathogens. Tick induced modulation of host immunity is increasingly recognized as an important factor in successful transmission or establishment of tick-borne pathogens. This study was conducted to determine the effects of repeated infestations with pathogen-free I. scapularis nymphs on in vitro proliferative responses of splenic lymphocytes from C3H/HeN mice. Lymphocytes from repeatedly infested and uninfested mice were exposed to concanavalin A (Con A), Escherichia coli Castellini & Chalmers lipopolysaccharide (LPS), or I. scapularis salivary gland soluble proteins (SGSP), to determine if lymphocyte responses differed between tick-exposed and nonexposed mice. Female C3H/HeN mice were infested one to four times with pathogen-free I. scapularis nymphs, with a 14-d tick-free period between each exposure. After each infestation, tick biology parameters were measured and lymphocyte proliferative responses assessed. Acquired resistance to I. scapularis was not evident in mice subjected to tick feeding. Significant differences in the responses of lymphocytes exposed to I. scapularis SGSP were observed between infested and noninfested mice. In contrast, few differences between infested and noninfested mice were evident for lymphocytes exposed to Con A or LPS. Our results suggest that repeated exposure to I. scapularis nymphs does not affect Con A or LPS-induced proliferation of splenic lymphocytes, but significantly effects lymphocyte responses to tick salivary gland antigens.

Animals↗

PubMed2000

Isolation and molecular cloning of a secreted immunosuppressant protein from Dermacentor andersoni salivary gland.

A 36-kDa immunosuppressant protein (Da-p36) was isolated from salivary glands of feeding female ixodid ticks Dermacentor andersoni, using its affinity for UltraLink Biosupport Medium (Pierce, Rockford, Illinois)/protein complexes. Using a nested set of forward degenerate oligonucleotide primers corresponding to Da-p36 N-terminal amino acids, a cDNA encoding the immunosuppressant protein was isolated by 3' rapid amplification of cDNA ends. The resulting 772-base pair cDNA encodes a novel protein with predicted molecular weight of 24.9 kDa. Sequence analysis revealed the presence of 5 potential glycosylation sites and 1 myristylation site. Immunoblot analyses showed native Da-p36 is present in salivary glands and saliva from both male and female D. andersoni but not in salivary glands or saliva from Amblyomma americanum or Ixodes scapularis. Reverse transcription polymerase chain reaction and immunoblot analyses showed that Da-p36 expression is temporally regulated in salivary glands with maximum mRNA levels preceding maximum Da-p36 accumulation that occurred at day 6 of feeding. The levels of Da-p36 mRNA and protein were greatly reduced in salivary glands from near-replete females removed from sheep after 8 days of feeding. These data are consistent with a role of Da-p36 in immunosuppression during feeding.

Amino Acid Sequence↗

PubMed1999

Ixodes scapularis: effects of repeated infestations with pathogen-free nymphs on macrophage and T lymphocyte cytokine responses of BALB/c and C3H/HeN mice.

Schoeler, G. B., Manweiler, S. A., and Wikel, S. K. 1999. Ixodes scapularis: Effects of repeated infestations with pathogen-free nymphs on macrophage and T lymphocyte cytokine responses of BALB/c and C3H/HeN mice. Experimental Parasitology 92, 239-248. Ixodes scapularis is the principal vector in the United States of Borrelia burgdorferi, the causative agent of Lyme borreliosis, the human granulocytic ehrichiosis agent, and Babesia microti. Infestation with I. scapularis nymphs has previously been shown to modulate host T lymphocyte cytokine production. Tick-induced host immunomodulation is increasingly recognized as a contributing factor in successful transmission and/or establishment of tick-borne pathogens. This study was conducted to determine the effects of repeated infestations with pathogen-free I. scapularis nymphs on the production of the macrophage cytokines interleukin (IL)-1beta and tumor necrosis factor-alpha and the T lymphocyte cytokines IL-2, IL-4, IL-10, and interferon-gamma in both BALB/c and C3H/HeN mice. The pattern of T lymphocyte cytokine production was evaluated to determine if repeated tick infestation polarizes the immune response toward a Th-1 or Th-2 cytokine profile. Female BALB/c and C3H/HeN mice were infested one to four times with pathogen-free I. scapularis nymphs, with a 14-day tick-free period between each exposure. After each infestation, tick biology parameters were measured and macrophage and T lymphocyte cytokine production was assessed. Elaboration of T lymphocyte and macrophage cytokines was quantitated by antigen capture enzyme-linked immunosorbent assay. Acquired resistance to I. scapularis feeding was not developed by either mouse strain. Significant differences in cytokine production were observed between infested and noninfested mice, as well as between the two mouse strains, following tick infestation. Infestation of both strains with pathogen-free I. scapularis results in a polarization of the host immune response toward a Th-2, anti-inflammatory pattern, with a corresponding suppression of Th-1 responses.

Animals↗

PubMed1999

Tick modulation of host immunity: an important factor in pathogen transmission.

Immunological interactions at the tick host interface involve innate and specific acquired host immune defenses and immunomodulatory countermeasures by the tick. Tick feeding stimulates host immune response pathways involving antigen-presenting cells, cytokines, B-cells, T-cells, circulating and homocytotropic antibodies, granulocytes, and an array of biologically active molecules. In response to host immune defenses, tick-mediated host immunosuppressive countermeasures inhibit: host antibody responses; complement activation; T-cell proliferation; and cytokine elaboration by macrophages and Th1-lymphocytes. Immunosuppressive proteins identified in tick salivary glands and saliva have been partially characterised. Tick-induced host immunosuppression facilitates blood meal acquisition and is an important factor in the transmission/establishment of the tick-borne disease-causing agent, Borrelia burgdorferi. A novel strategy for control of tick-borne pathogens is proposed.

Animals↗

PubMed1999

Identification, characterization, and expression of three new members of the Borrelia burgdorferi Mlp (2.9) lipoprotein gene family.

We previously reported on the existence of a family of lipoprotein genes, designated 2.9 lipoprotein genes, encoded in at least seven versions on the circular (supercoiled) cp32 and cp18 plasmids of Borrelia burgdorferi 297. A distinguishing feature of the 2.9 lipoproteins were highly similar signal sequences but variable mature polypeptides that segregated into two antigenic classes. Further screenings of B. burgdorferi 297 genomic libraries led to the identification of three additional 2.9 lipoprotein genes, renamed herein mlp, for multicopy lipoprotein genes. Computer analyses and immunoblotting revealed that Mlp-9 segregated with the antigenic class I lipoproteins, whereas Mlp-8 and Mlp-10 were members of class II. Northern blotting showed that all three of the mlp genes were expressed when B. burgdorferi was cultivated in vitro at 34 degrees C, although mlp-9 and mlp-10 transcripts were expressed at very low levels. Additional combined immunoblotting and comparative reverse transcription-PCR analyses performed on borreliae cultivated in vitro at 23, 34, or 37 degrees C indicated that although Mlp-8 was substantially more abundant than Mlp-9 or Mlp-10, all three of the mlp genes were upregulated during B. burgdorferi replication at 37 degrees C. Expression of the same three lipoproteins was further enhanced upon growth of the spirochetes within dialysis membrane chambers (DMCs) implanted intraperitoneally in rats (i.e., spirochetes in a mammalian host-adapted state), suggesting that temperature alone did not account for maximal upregulation of the mlp genes. That certain mlp genes are likely expressed during the growth of B. burgdorferi in mammalian tissues was supported by findings of antibodies against all three Mlp lipoproteins in mice after challenge with Ixodes scapularis nymphs harboring B. burgdorferi 297. The combined data suggest that as opposed to being differentially expressed in any reciprocal fashion (e.g., OspA/OspC), at least three mlp genes are simultaneously upregulated by temperature (37 degrees C) and some other mammalian host factor(s). The findings have importance not only for understanding alternative modes of differential antigen expression by B. burgdorferi but also for assessing whether one or more of the Mlp lipoproteins represent new candidate vaccinogens for Lyme disease.

Animals↗

PubMed1998

Characterization of an immunosuppressant protein from Dermacentor andersoni (Acari: Ixodidae) salivary glands.

A 36-kDa soluble protein was found in the salivary glands of female Dermacentor andersoni (Stiles) ticks that suppressed the in vitro proliferative response of murine splenocytes to concanavalin A (Con A). Incubating the purified protein with splenocytes reduced the incorporation of thymidine into the DNA of proliferating T-lymphocytes by more than 90% compared with cells exposed to Con A and buffer alone. The N-terminal amino acid sequence of the immunosuppressant protein was determined to be NH2-Leu-His-Lys-Ala(Asp)-Lys-Ile-Val-Lys-Leu-Thr -Glu-Glu-Ala -Arg-Lys-Tyr-Val-Gly-Arg-Xxx-Xxx-Thr-Thr-Ala-Leu-Gly-. Although the sequence exhibited a modest degree of similarity with a segment of immunoglobulin-binding protein found in several species of mammals, the mode of action of the immunosuppressant protein is unknown. This protein may play an important role in suppressing the host's acquisition of resistance to ticks.

Amino Acid Sequence↗