Structural Basis for Antigen Recognition by Transglutaminase 2-specific Autoantibodies in Celiac Disease

Antibodies to the autoantigen transglutaminase 2 (TG2) are a hallmark of celiac disease. We have studied the interaction between TG2 and an anti-TG2 antibody (679-14-E06) derived from a single gut IgA plasma cell of a celiac disease patient. The antibody recognizes one of four identified epitopes targeted by antibodies of plasma cells of the disease lesion. The binding interface was identified by small angle x-ray scattering, ab initio and rigid body modeling using the known crystal structure of TG2 and the crystal structure of the antibody Fab fragment, which was solved at 2.4 Å resolution. The result was confirmed by testing binding of the antibody to TG2 mutants by ELISA and surface plasmon resonance. TG2 residues Arg-116 and His-134 were identified to be critical for binding of 679-14-E06 as well as other epitope 1 antibodies. In contrast, antibodies directed toward the two other main epitopes (epitopes 2 and 3) were not affected by these mutations. Molecular dynamics simulations suggest interactions of 679-14-E06 with the N-terminal domain of TG2 via the CDR2 and CDR3 loops of the heavy chain and the CDR2 loop of the light chain. In addition there were contacts of the framework 3 region of the heavy chain with the catalytic domain of TG2. The results provide an explanation for the biased usage of certain heavy and light chain gene segments by epitope 1-specific antibodies in celiac disease.     

A new acroeimerian (Apicomplexa: Eimeriidae) in spotted house gecko,Gekko monarchus (Schlegel) (Sauria: Gekkonidae) from Peninsular Malaysia

Systematic Parasitology - A new species of Acroeimeria Paperna & Landsberg, 1989 is described from the spotted house gecko, Gekko monarchus (Schlegel) from Peninsular Malaysia. Oöcysts...     

Cross-transmission studies with Eimeria arizonensis, E. arizonensis-like oocysts and Eimeria langebarteli: host specificity at the genus and species level within the Muridae

Cross-transmission experiments were done using sporulated oocysts of Eimeria arizonensis from Peromyscus truei and Peromyscus maniculatus, and oocysts of 2 putative species that resemble E. arizonensis, i.e., Eimeria albigulae from Neotoma albigula, and Eimeria onychomysis from Onychomys leucogaster. Oocysts of each species were inoculated into representatives of P. maniculatus and the latter 2 rodent species. Other experiments were conducted wherein oocysts of Eimeria langebarteli from Peromyscus leucopus were given to P. truei and P. maniculatus. Oocysts of E. arizonensis from P. truei and P. maniculatus could be transmitted only to P. maniculatus; likewise, oocysts of E. albigulae and E. onychomysis produced patent infections only in N. albigula and O. leucogaster, respectively. Oocysts of E. langebarteli from P. leucopus could be transmitted to P. truei, but not P. maniculatus. These results indicate that E. arizonensis, and the morphologically similar E. albigulae and E. onychomysis, are distinct species that are not transmissible between the genera of their respective hosts (Peromyscus, Neotoma, Onychomys), and that some isolates of E. langebarteli, reported from 6 species of Peromyscus and Reithrodontomys megalotis, may not always be infective to P. maniculatus.     

<Emphasis Type="Italic">Eimeria maricopensis</Emphasis> n. sp. (Apicomplexa: Eimeriidae) from the Arizona cotton rat <Emphasis Type="Italic">Sigmodon arizonae</Emphasis> Mearns (Rodentia: Cricetidae) in central Arizona,USA

Eimeria maricopensis n. sp. (Apicomplexa: Eimeriidae) is described from 2 of 15 (13%) Arizona cotton rats Sigmodon arizonae Mearns in Arizona, USA. Sporulated oöcysts of this new species are ovoidal to ellipsoidal, 20–28 × 16–22 (24.9 × 19.2) µm, with a smooth, bi-layered wall; both micropyle and oöcyst residuum are absent, but fragmented polar granule material is present. Sporocysts are ellipsoidal, 11–14 × 6–8 (12.9 × 7.0) µm, with a Stieda body, sub-Stieda body, and sporocyst residuum; sporozoites are elongate with a spheroidal anterior refractile body and a subspheroidal posterior refractile body. In addition, sporulated oöcysts of Eimeria sigmodontis Barnard, Ernst & Dixon, 1974, Eimeria tuskegeensis Barnard, Ernst & Dixon, 1974 and Eimeria webbae Barnard, Ernst & Dixon, 1974 are described from S. arizonae. This is the first report on the coccidia of S. arizonae.     

A new caryosporan (Apicomplexa: Eimeriidae) from flat-headed snake,Tantilla gracilis (Reptilia: Ophidia: Colubridae), from McCurtain County,Oklahoma, USA

The flat-headed snake, Tantilla gracilis Baird and Girard is a small reptile belonging to the family Colubridae. Feces from a single T. gracilis from McCurtain County, Oklahoma, USA, was collected and examined for coccidia; it was found to be passing a new species of Caryospora. Oöcysts of Caryospora sargentae n. sp. are spheroidal to typically subspheroidal with a moderately-pitted bi-layered wall, measure (L × W) 20.7 × 19.2 µm, and have a length/width (L/W) ratio of 1.1; a micropyle and oöcyst residuum were absent but one to several small, irregular to spheroidal masses of non-refractile debris within the oocyst was present as well as a polar granule attached to the inner oöcyst wall. Sporocysts are ovoidal and measure 15.0 × 11.0 µm, L/W 1.4; a nipple-like Stieda body is present as well as a distinct rounded sub-Stieda body. The sporocyst residuum is composed of a large, dense, irregular mass of various sized granules located between and often obscuring the sporozoites. This is the third coccidian described from the flat-headed snake. In addition, we include some data on the endogenous development of the coccidian.