Comparative analysis of adaptive immune receptor loci in mammalian species

The process of binding and neutralizing an antigen primarily relies on the production of adaptive immune receptors: immunoglobulins (IG) and T-cell receptors (TCR). Unlike other proteins, these receptors are not directly encoded in the germline genome. Instead, they originate from a complex of somatic processes collectively known as V(D)J recombination, assignable for merging one V, one D, and one J gene within the single adaptive immune locus.

Various existing studies report extreme diversity of antibodies and T-cell receptors. Recent immunogenomics studies increased both the volume and the quality of genomic and transcriptomic data, highlighting a need for comparative studies across species, orders, and classes. To overcome this gap, we performed the first comparative analysis of full-length sequences of IG/TR loci across 46 mammalian species from 13 taxonomic orders. Germline gene counts were shown to correlate in Ig heavy (IGH) / Ig lambda (IGL) loci, though anticorrelate in Ig kappa (IGK) / IGL, possibly indicating coevolution between corresponding chains. Moreover, structures of Ig/TCR loci were analyzed, and it was shown that loci formed by long arrays of high multiplicity repeats are more common for species that have experienced population bottlenecks. Haplotypes of IG/TCR loci with low similarity within a species were found, suggesting that they may have a limited potential for homologous recombination.

Further analysis of a mammalian clade revealed the elongated and cysteine-rich D gene in the IGH of some species. The V gene count and homology in reliance on the length of such cysteine-rich D genes indicates the possibility of distinct evolutionary pressure and development of V and D genes within individual species. This presentation will summarize the findings of both studies and show the benefits of large-scale comparative immunogenomics analysis.