Nonhuman Primate IgA: Genetic Heterogeneity and Interactions with CD89

Abstract

Nonhuman primates are extremely valuable animal models for a variety of human diseases. However, it is now becoming evident that these models, although widely used, are still uncharacterized. The major role that nonhuman primate species play in AIDS research as well as in the testing of Ab-based therapeutics requires the full characterization of structure and function of their Ab molecules. IgA is the Ab class mostly involved in protection at mucosal surfaces. By binding to its specific Fc receptor CD89, IgA plays additional and poorly understood roles in immunity. Therefore, Ig heavy α (IGHA) constant (C) genes were cloned and sequenced in four different species (rhesus macaques, pig-tailed macaques, baboons, and sooty mangabeys). Sequence analysis confirmed the high degree of intraspecies polymorphism present in nonhuman primates. Individual animals were either homozygous or heterozygous for IGHA genes. Highly variable hinge regions were shared by animals of different geographic origins and were present in different combinations in heterozygous animals. Therefore, it appears that although highly heterogeneous, hinge sequences are present only in limited numbers in various nonhuman primate populations. A macaque recombinant IgA molecule was generated and used to assess its interaction with a recombinant macaque CD89. Macaque CD89 was able to bind its native ligand as well as human IgA1 and IgA2. Presence of Ag enhanced macaque IgA binding and blocking of macaque CD89 N-glycosylation reduced CD89 expression. Together, our results suggest that, despite the presence of IgA polymorphism, nonhuman primates appear suitable for studies that involve the IgA/CD89 system.

Mucosal Immunoglobulins

“…Allelic polymorphisms of Cα genes have been reported in humans (Hendriks et al, 1988;Bottaro et al, 1989), nonhuman primates (Scinicariello and Attanasio, 2001;Scinicariello et al, 2006;Rogers et al, 2008), horses (Wagner et al, 1997), cattle (Knight et al, 1988;Brown et al, 1997), pigs (Brown et al, 1995), sheep (Zhou et al, 2005), goats (Zhou et al, 2006), dogs (Peters et al, 2004), and mice (Phillips-Quagliata, 2002). As mentioned earlier, the hinge region is a major site of such variation.…”

“…The most outstanding difference is seen in the hinge region (only 18% homology). Indeed, the hinge region is a source of major heterogeneity in nonhuman primate IgA (Rogers et al, 2008). Allelic variation is also seen in the hinge of dog IgA (Peters et al, 2004), sheep IgA (Zhou et al, 2005), goat IgA (Zhou et al, 2006), mouse IgA (PhillipsQuagliata, 2002), and pig IgA (Brown et al, 1995).…”

“…The genes for the heavy chain of IgA have been cloned from several species, including humans (Flanagan et al, 1984), nonhuman primates (Kawamura et al, 1989(Kawamura et al, , 1990Ueda et al, 1988;Scinicariello et al, 2006;Rogers et al, 2008), rodents (Tucker et al, 1981;Bruggemann et al, 1986), bats (Butler et al, 2011), pets and domesticated animals (Knight et al, 1988;Burnett et al, 1989;White et al, 1998;Brown and Butler, 1994;Wagner et al, 1997;Patel et al, 1995;Zhou et al, 2006), dolphins (Mancia et al, 2007), marsupials (Aveskogh and Hellman, 1998), monotremes (Belov et al, 2002;Vernersson et al, 2010), and birds (Mansikka, 1992;Magor et al, 1998;Choi et al, 2010;Huang et al, 2012;Guo et al, 2014), in some cases as part of species genome projects. Thus, DNA sequence information for IgA is available for a wide range of mammalian and an increasing number of bird species.…”

Coevolution of Mucosal Immunoglobulins and the Polymeric Immunoglobulin Receptor: Evidence That the Commensal Microbiota Provided the Driving Force

“…Mapping of IGH loci has now been completed for a number of primate species, including human (Homo sapiens), gorilla (Gorilla gorilla), chimpanzee (Pan troglodytes), orangutan (Pongo pygmaeus), gibbon (Hylobates lar), baboon (Papio anubis), mangabey (Cercocebus torquatus atys), and three species of macaques, the crab-eating monkey (Macaca fascicularis), pig-tailed monkey (Macaca nemestrina), and rhesus monkey (Macaca mulatta) [93][94][95][96][97]. A distinguishing feature of primates in the family Hominidae (great apes, including humans, gorillas, chimpanzees, and orangutans) and the family Hylobatidae (gibbons) is the presence of two IgA subclasses.…”

Immunotherapy of Tuberculosis with IgA and Cytokines

“…Evaluation of 2E9IgA based CIT in non-human monkey models of TB. Macaques are eminently suitable, since they express the IgA/CD89 receptor [78] that can bind human IgA [79]. A suitable technique for aerosol delivery of IgA would need to be developed using the approaches for the inhaled therapy with various agents [80].…”