Abstract
CD94 forms heterodimers with NKG2A, -C, or –E to constitute lectin-like natural killer cell receptors for MHC-E. Its structure differs from other C-type lectins in that the second α-helix is replaced by a loop that forms the interacting interface with the NKG2 molecules. Although CD94 has remained highly conserved mammals, several alternative splicing variants have been detected in some species. To evaluate the prevalence and significance of this phenomenon, we have cloned and sequenced CD94 cDNAs in six species of New World primates from the Cebidae and Atelidae families. Full-length sequences had a mean similarity of 96 % amongst New World primates and of 90 % to the human orthologue, with little variation in the residues interacting with NKG2 or MHC-E molecules. Despite this high conservation, a total of 14 different splice variants were identified, half of which were shared by two or more primate species. Homology-based modeling of the C-type lectin domain showed that most isoforms folded stably, although they had modifications that prevented its interaction with NKG2 and MHC-E. Two isoforms were predicted to replace the typical CD94 loop by a second α-helix, evidencing a domain fold transition from a CD94 structure to a canonical C-type lectin. These two structures were more similar to members of the CLEC lectin family than to the native CD94. Thus, CD94 has remained conserved in primates to maintain functional interactions with NKG2 and MHC-E, while at the same time has diversified by alternative splicing potentially providing additional functional scenarios.
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Acknowledgments
This work was supported by a grant from the Universidad Nacional de Colombia’s Research Division to LFC. Colombia’s Ministry of the Environment and Sustainable Development authorized the access to genetic resources for scientific research without commercial interests (contract No. 1 of 2012).
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Nucleotide sequence data reported are available in the GenBank database under accession numbers JX170717-JX170743
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Galindo, J.A., Cadavid, L.F. High diversification of CD94 by alternative splicing in New World primates. Immunogenetics 65, 281–290 (2013). https://doi.org/10.1007/s00251-013-0685-x
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DOI: https://doi.org/10.1007/s00251-013-0685-x