Trichinella antigens: a review María A. Dea-Ayuela, Francisco Bolas-Fernández
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María A. Dea-Ayuela, Francisco Bolas-Fernández. Trichinella antigens: a review. Veterinary Research, BioMed Central, 1999, 30 (6), pp.559-571. hal-00902596
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Trichinella antigens: a review
María A. Dea-Ayuela Francisco Bolas-Fernández
Dcpartamento de Paraaitología, Facultad de Farmacia. Univerxidad Cornplutense, 28040 Madrid, Spain
(Received 4 March 1999; accepted 27 July !999)
Abstract-This paper presents a review ol’the Trichinella antigens within the context of spccics vari- ation. As with other parasites, Trichinella antigens can he classified according to their localisation as surface, excretory/secretory (ES) and somatic components. Surface antigens are mainly constitucnts of the outer cuticle although secrctions from inner parts of the body wall as well as from the oesoph- agus can temporarily accumulate in the surface. ES antigens come mainly from the excretory gran- ules of the stichosome, whereas somatic constitutive antigens anne from the internal parts of the worms. ES products arc considered very important from an immunological point of view as they are easily targeted by the immune system, whereas parasite death is required for exposure of somatic products. Some of the antigenic components have been characterised chemically. Phosphorylcholine is an important hapteii that modulatcs the immunc responses in Trichinella infections. Glycopi-oteins are the major components of surface and excretory/secretory products. A 43-kDa glycoprotein has been regarded as a good candidate for diagnosis and vaccination purposes. Recently some glycans have received special attention either as relevant epitopes or as parasite evasion strategies. © l ni;1/El;evier, Paris.
Trichinella / antigen / phosphorylcholine / glycoprotein / carbohydrate
Résumé - Antigènes de Trichinella : une revue. Cette revue concerne les antigènes de 7’riolrinella dans le contexte des variations d’espèces. Comme dans le cas d’autres parasitcs, les antigènes de Trichinc·llu peuvent être classés en fonction de leur localisation comme composants somatiques, de surface et d’excrétion-sécrétion (ES). Les antigènes de surface sont principalement des constituants de la cuticule externe, bien que les sécrétions des parties internes de la paroi corporelle ainsi que celles de i’œsophage s’accumulent parfois temporairement à la surface. Les antigènes d’excrétion- sécrétion proviennent principaleinent des granules excrétoires du stichosome tandis quc les anti- gènes somatiques constitutifs appartiennent aux parties intcrncs des vers. On considère que les pro- duits d’exci-étion-séci-étioti sont très importants du point de vue inununolo!tique car ils sont tacitement accessibles par le système immunitaire tandis que la mort du parasite est nécessaire pour que les produits somatiques soient exposés. Quelques-uns des composants antigéniques ont été caractérisés.
!: Correspondence and reprints Tel.: (34) 1 394 1918; fax: (34) 1 394 18 I5; c-mail: holts(a)euciyiax.siiii.LICIII.CS la phosphorylcholine est un haptène important qui module les réponses immunitaires dans les infec- tions par Trichinella. Les glycoprotéines sont les composants majeurs des antigènes de surface et des produits d’excrétion-sécrétion. La glycoprotéine de 43 kDa a été considérée comme un bon candidat pour le diagnostic et pour les projets de vaccination. Récemment, quelques glycanes ont été l’objet d’une attention spéciale soit dans le cadre de la stratégie d’évasion des parasites soit parce qu’ils ont été considérés comme des épitopes appropriés. © Inra/Elsevier, Paris.
Trichinella / antigène / phosphorylcholine / glycoprotéine / carbohydrate
1. INTRODUCTION the surface, the excretory/secretory (ES) and residual somatic components. Trichinella worms are adenophorean It is assumed that surface antigens are nematodes whose life endogenous cycles the most important targets for the immune involve the intestines, blood successively system because they provide a host-para- and muscles. This particular life cycle, site interface but it has also been shown that intra- and extra-cellular including stages, internal antigens can be expressed in the active interactions promotes host-parasite outer cuticle thus mimicking those of surface thus the facilitating antigen recognition by origin. Secreted antigens can also favour host immune system. The immune response parasite survival by blocking the immune Trichinella has been studied against widely system of the host [42]. in both natural and experimental infections and the major interest has focused on rele- Chemical characterisation of Trichinella vant epitopes capable of eliciting responses antigens has been attempted extensively. that are protective against reinfections or of Among the surface and ES products, gly- interest for diagnostic purposes. Some of coproteins are the major components. Char- them are stage specific. Furthermore, it is acterisation of their fine structure, localisa- likely that the parasite antigens play an tion and their potential function have been important role in parasite protection against the subject of many studies over the last few the host environment along the successive years. Phosphorylcholine (PC) is a very con- steps of its life cycle, in addition to served and widely distributed molecule in immunostimulatory effects in the hosts. As nature and its presence in the somatic com- in other helminth species, Trichinella anti- ponents of Trichinella is also well docu- gens can be divided into three components: mented. 2. ANTIGENS ACCORDING from the interaction of the 40- and 20-kDa TO THEIR ANATOMIC bands, whereas the presence of the 58-kDa LOCALISATION homologue dimer is a characteristic of the NBL stage [41 ]. 2.1. Surface antigens Monoclonal antibodies have been very useful for surface antigen identification. Evidence that the host synthesises anti- Ortega-Pierres et al. [62] prepared seven monoclonal antibodies named NIM-M 1 to bodies against different cuticular compo- NIM-M7. Monoclonal antibodies NIM-M5 nents has primarily been shown by using and NIM-M6 reacted with the 64-kDa band whole parasites and techniques such as indi- solubilised from the rect immunofluorescence [16, 90]. Electron NBL, although only microscope and ferritin-labelled conjugates the NIM-M5 was able to react with the sur- face of the live NBL. Additional bands of [221 as well as scanning microscopy have 58, 34 and 30 kDa culture, shown precipitated antibodies on the larval appeared during whereas the of the NIM-M5 for the and adult surface. !z51-labelled surface pro- affinity teins have been solubilised in 2 % SDS, then NBL surface decreased. By in vivo labelling of NBL, L and adults in culture, the authors immunoprecipitated with rat immune serum and resolved in SDS-PAGE followed by observed shedding of the surface compo- autoradiography. The new-born larvae nents that were replaced by new ones, con- (NBL) exhibited four other major antigens cluding that the removal of surface compo- nents could be the mechanism which the of 20, 30, 58 and 64 kDa, whereas the mus- by cle larvae (L1) exhibited four major anti- immune system recognises epitopes usually hidden in the intact worm. The monoclonal gens of 47, 55, 90 and 105 kDa, of which the 55- and 105-kDa antigens have lentil antibody NIM-M 1 recognised four surface on the L that share lectin binding capacities. Another group of antigens indicating they common Monoclonal NIM-7 antigens was identified in the cuticle of the epitopes. reacted with the male L2-L4 stages with molecular weights of 20, mainly copulatory 33, 40 and 56 kDa. Amongst these antigens boursa and slightly with some other areas of the male and female thus the 56 kDa was different from the 55 kDa of surfaces, sug- a of surface the L I. Furthermore, among the antigens gesting regional specialisation It was concluded present in the L4 stage, only those of low antigens [63]. by peptide that all surfaces come molecular weight were shared with the adult analysis proteins may from the same which are built on stage 169, 70]. The authors also observed gene, up labelled surface antigens secreted into the the surface as monomeric or dimeric either culture medium. Changes in the molecular unglycosylated or glycosylated forms. Large amounts of were surface during culture time were observed partially purified antigens obtained treatment of L1 with cationic by Makenzie et al. [53 These changes were by and to be later assessed by Jungery et al. [41 ] where detergents appeared highly pro- tective as assessed immunisation only one single 64-kDa component was by assays [35] . identified on the surface of NBL following 2.5 or 6.5 h of culture. After 17.7 h or Immunocytochemical studies using the 1 night of culture, additional bands of 58, monoclonal antibody NIM-M1 have shown 34 and 32 kDa were also present. By using that surface and protective antigens origi- the same technique, Parkhouse and Ortega- nate in the stichosome of the larvae [56, 64] Pierres [66] obtained similar results regard- and more precisely in the a-granules 192, ing the L 1 stage, with slight differences for 94]. According to these last authors, the a- the NBL and the adult stages (64, 58, 34 granules are the main source of surface anti- and 30 kDa and 40, 33 and 20 kDa, respec- gens which would then be secreted via the tively). In the adult, a 60-kDa band resulted oesophagus. Eleven groups of antigens rang- ing from 32 to 220 kDa were identified by ules (a0/al, a2, (5 and y or a, (3, Y and 8) Boireau et al. [7] based on antigen recog- have been described in the L 1 stage [81, nition by a panel of monoclonal antibodies 93]. The 50-55-kDa antigens are secreted raised against larval extracts. Antigens from by a-stichocytes, whereas the 48-kDa anti- groups 1, 2, 3, 4 and 6 are localised in either gen is present in (3-stichocytes [84]. It is not the cuticle, oesophagus or longitudinal clear whether the various antigen locations bands, whereas those of groups 5 and 7, within the stichosome are due to different apart from the cuticle and some parts of the structures or whether they come from a com- oesophagus, are present in the hypodermis, mon precursor which undergoes post-trans- haemolymph and genital primordium of the lational changes in different regions of the larva and adult stages. Some antigens from stichosome. It was also observed that NBL groups 1, 2 and 3 are not present in the adult start to form the stichosome and secretory stage, thus indicating a loss of epitopes dur- granules soon after invasion of the muscle ing cuticle shedding after the first moult. cells [33]. At least 28 bands with molecular weights ranging from 11 to 200 kDa were seen in 2.2. Excreted/Secreted (ES) antigens the S3 fraction by SDS-PAGE analysis [21 )] and 37 bands (22 of which contained car- The first evidence of the presence of anti- bohydrates) by isoelectrofocusing. Twenty of the S3 were identified as gens in the excreted/secreted products from components and then various stages of 7&dquo;nc’/!
Recently, the Trichinella genus has been resolved into five species (T. spiralis, T. 3.3. The 43-kDa glycoprotein britovi, T. nativa, T. nelsoni and T. pseu- dospiralis), and three related gene pools (T5, T6 and T8) [71 J, of various distribu- Among the TSL-1 group of Trichinella tions and host range. Biochemical differ- antigens, the 43-kDa glycoprotein is one of ences between these rel- the most intensely investigated. In 1990 species involving evant have been shown [1, 89]. A Gold et al. [33], were able to separate a 43- antigens correlation between surface vari- kDa antigenic protein by chromatographic techniques ation and has been found that, after gave rise to a geographical origin deglycosylation, in T nativa and T. that influences 32-kDa which was not spiralis polypeptide recog- marked differences nised by antibodies generated against the infectivity [8J. Similarly, were observed between the of T. native Studies were conducted infectivity protein. by and T5 that correlated with varia- Vassilatis et al. [100-102] who cloned the spiralis tions in DNA of cDNA of the protein secreted by T. sl)iralis complementary sequences the 49/43- or 53-kDa from muscle larvae. Further analysis of the 344- 46-, antigens both [ 109]. variation was aminoacid-deduced sequence revealed: i) species Antigenic also observed at the level as the presence of two infra-specific potential N-glycosyla- shown the differences in tion links at positions 24 and 117; and ii) by antigen recog- nition immune sera infec- the of two patterns by against presence strongly amphipathic tions different isolates of helices a motif. by geographical confirming helix-loop-helix T. These and Antibodies raised the recombinant spiralis [9, 25, 34]. specific against variations have the native form infra-specific important protein recognised purified in the of trichinel- and two additional bands under both glyco- implications serodiagnosis losis [10, 29, 32, 72]. sylated and deglycosylated forms. It was concluded that either different variants of Monoclonal antibodies have been very the 43-kDa proteins with a different C-ter- useful not only for antigen purification but minal exist or that different proteins share also for species and isolate identification. the same immunological epitope. Antibod- Monoclonal antibodies have been generated ies against the 43-kDa purified glycopro- that recognise antigens present in T. pseu- tein recognised the 81-120- and 121-160- dospiralis but not in T. spiralis [104J or that mer non-protective synthetic peptides, recognise seven components (between 45 whereas it failed to recognise the 40-80- and 105 kDa) of the T. 5j)iralis larval crude mer protective peptide, again suggesting extract and only five in T pseudospiralis. that the epitopes of this region in the native The close relationships between T. britovi molecule may be masked by carbohydrates and T5 and between T .>.pirali.>. and T. nativa [77]. were confirmed by Boireau et al. [7 ] using a large panel of monoclonal antibodies. 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