Structural analysis of effector functions related motifs, complement activation and hemagglutinating activities in Lama glama heavy chain antibodies

Saccodossi, Natalia; Simone, Emilio A. De; Leoni, Juliana

doi:10.1016/j.vetimm.2011.12.001

Cited by 10 publications

(8 citation statements)

References 36 publications

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“…In Arabian camel, three IGHG genes have been identified (IMGT Repertoire (IG and TR) > Gene table > Gene table: Arabian camel ( Camelus dromedarius ) IGHC) 1 . Four IGHG genes ( IGHG1A , IGHG1B , IGHG2B, and IGHG2C , these last two genes without CH1 in the alpaca genome) are present in the alpaca and llama genomes (Achour et al, 2008; Henry et al, 2019) (IMGT Repertoire (IG and TR) > Gene table > Gene table: Alpaca (Vicugna pacos) IGHC) 1 , even if other studies have also identified IGHG2A and IGHG3 genes in the expressed IgG repertoire of llama (De Genst et al, 2006; Saccodossi et al, 2012).…”

Section: The Camel Immunoglobulin: a Dichotomous Adaptive Humoral Immmentioning

confidence: 99%

The Camel Adaptive Immune Receptors Repertoire as a Singular Example of Structural and Functional Genomics

Ciccarese

Burger²,

Ciani

et al. 2019

Front. Genet.

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The adaptive immune receptors repertoire is highly plastic, with its ability to produce antigen-binding molecules and select those with high affinity for their antigen. Species have developed diverse genetic and structural strategies to create their respective repertoires required for their survival in the different environments. Camelids, until now, considered as a case of evolutionary innovation because of their only heavy-chain antibodies, represent a new mammalian model particularly useful for understanding the role of diversity in the immune system function. Here, we review the structural and functional characteristics and the current status of the genomic organization of camel immunoglobulins (IG) or antibodies, α/ß and γ/δ T cell receptors (TR), and major histocompatibility complex (MHC). In camelid humoral response, in addition to the conventional antibodies, there are IG with “only-heavy-chain” (no light chain, and two identical heavy gamma chains lacking CH1 and with a VH domain designated as VHH). The unique features of these VHH offer advantages in biotechnology and for clinical applications. The TRG and TRD rearranged variable domains of Camelus dromedarius (Arabian camel) display somatic hypermutation (SHM), increasing the intrinsic structural stability in the γ/δ heterodimer and influencing the affinity maturation to a given antigen similar to immunoglobulin genes. The SHM increases the dromedary γ/δ repertoire diversity. In Camelus genus, the general structural organization of the TRB locus is similar to that of the other artiodactyl species, with a pool of TRBV genes positioned at the 5’ end of three in tandem D-J-C clusters, followed by a single TRBV gene with an inverted transcriptional orientation located at the 3’ end. At the difference of TRG and TRD, the diversity of the TRB variable domains is not shaped by SHM and depends from the classical combinatorial and junctional diversity. The MHC locus is located on chromosome 20 in Camelus dromedarius. Cytogenetic and comparative whole genome analyses revealed the order of the three major regions “Centromere-ClassII-ClassIII-ClassI”. Unexpectedly low extent of polymorphisms and haplotypes was observed in all Old World camels despite different geographic origins.

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Section: The Camel Immunoglobulin: a Dichotomous Adaptive Humoral Immmentioning

confidence: 99%

The Camel Adaptive Immune Receptors Repertoire as a Singular Example of Structural and Functional Genomics

Ciccarese

Burger²,

Ciani

et al. 2019

Front. Genet.

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“…The CFT is based on the use of the complement cascade, a critical component of the innate immune system for eliminating invading pathogens (Alhabbab, 2018). This mechanism is triggered by the interaction of a protein complex known as a Cq1 binding site with the CH2 domain of an antibody (Saccodossi et al., 2012). The antigen used in the CFT binds to target antibodies in test sera and forms antibody‐antigen complexes that bind complement, thus preventing the lysis of ovine erythrocytes by complement.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of three immunological assays to mitigate the risk of transboundary spread of Coxiella burnetii by alpacas

Tellis

Rowe

Coilparampil

et al. 2021

Transbounding Emerging Dis

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Coxiella burnetii causes coxiellosis in animals and Q fever in humans, a potentially debilitating zoonotic disease commonly transmitted through domestic ruminants. To prevent transboundary spread of C. burnetii, animals may be tested prior to export. In alpacas, this process is complicated by the lack of scientific evidence for C. burnetii infection in the species, and the unique composition of camelid antibodies, which may cause false‐positive results in assays developed for ruminants. We evaluated a complement fixation test (CFT; currently recommended for alpacas in New Zealand), an enzyme‐linked immunosorbent assay (ELISA) and an immunofluorescence assay (IFA). Positive analytical control samples were generated through vaccination of alpacas with a human Q fever vaccine, whereas negative analytical control samples were sourced from New Zealand (deemed free of C. burnetii). Immunological assays were conducted on 131 alpaca sera submitted for export testing. Test characteristics (sensitivity, specificity, positive and negative predictive values) for CFT, ELISA and IFA were determined using Bayesian latent class analysis. Due to anticomplementary activity, 37 (28.2%) of the CFT results were inconclusive, making CFT unsuitable for routine use. Of the remaining 94 samples, 10.6%, 0% and 7.4% were positive for C. burnetii antibodies based on CFT, ELISA and IFA, respectively, yielding estimated sensitivities of 58%, 26% and 78%, and estimated specificities of 95%, 98% and 95%, with the estimates for sensitivity being imprecise, as evidenced by wide 95% credible intervals. Positive predictive values were similar across assays, albeit very low at the estimated seroprevalence of 5%. Our results indicate that, of the tests available, IFA appears to be the most appropriate for use in alpacas. Higher sensitivity of antibody detection, use of antigen detection assays and availability of samples from individuals with evidence of infection could provide additional insight into the risk of transboundary spread of C. burnetii by alpacas.

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“…Además nosotros no fuimos capaces de demostrar funciones efectoras como fijación de complemento por parte de los HCAbs, cuando las Igs convencionales tienen sitios de fijación para C1q, (Saccodossi et al, 2012). Otro estudio demostró que los HCAbs no aparecen en las respuestas inmunes de manera temprana sino luego de la acción de IgG1 (De Simone et al, 2008).…”

Section: Conclusiónunclassified

Caracterización de IgM, IgG Total, IgG1 y anticuerpos de cadena pesada en calostro de llamas ("Lama glama") mediante Elisa

Caggiano¹,

Saccodossi

Gentile

et al. 2014

Revista Complutense De Ciencias Veterinarias

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RESUMENObjetivos: determinar los niveles de IgM, IgG total y Anticuerpos de Cadena Pesada (HCAbs; por su sigla en inglés Heavy Chain Antibodies) (IgG2 e IgG3) en calostro de llamas y evaluar la concentración de HCAbs en relación a la IgG total y al isotipo convencional IgG1.Métodos: en este estudio se utilizaron 15 llamas preñadas, que fueron ordeñadas dentro de las primeras 24 horas post-parto. Se diseñaron ELISAs Sandwich para la cuantificación de IgM total, IgG total e IgG1. La concentración de HCAbs fue calculada mediante la diferencia entre IgG total e IgG1. (HCAbs =IgG total-IgG1).Resultados: los niveles encontrados fueron: IgM=17.02 mg/ml (DS=9.85) IgG total= 42.54 mg/ml (DS=27.79), IgG1=24.34 mg/ml (DS=13.96) y HCAbs (IgG total-IgG1)= 18.19 mg/ml (DS=15.49). Los resultados de IgG fueron consistentes en relación a lo descripto en otras especies con similar tipo de placentación. Los HCAbs representan el 43% de IgG calostral y la concentración de IgM presentó valores muy altos (dos y tres veces más elevados) que los descriptos en las especies con similar tipo de placentación.

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Structural analysis of effector functions related motifs, complement activation and hemagglutinating activities in Lama glama heavy chain antibodies

Cited by 10 publications

References 36 publications

The Camel Adaptive Immune Receptors Repertoire as a Singular Example of Structural and Functional Genomics

The Camel Adaptive Immune Receptors Repertoire as a Singular Example of Structural and Functional Genomics

Evaluation of three immunological assays to mitigate the risk of transboundary spread of Coxiella burnetii by alpacas

Caracterización de IgM, IgG Total, IgG1 y anticuerpos de cadena pesada en calostro de llamas ("Lama glama") mediante Elisa

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