A unique T cell receptor discovered in marsupials

Abstract

T cells recognize antigens by using T cell receptors (TCRs) encoded by gene segments, called variable (V), diversity (D), and joining (J), that undergo somatic recombination to create diverse binding specificities. Four TCR chains (␣, ␤, ␥, and ␦) have been identified to date, and, as T cells develop in the thymus, they express exclusively either an ␣␤TCR or a ␥␦TCR heterodimer. Here, we show that marsupials have an additional TCR (TCR) that has V, D, and J that are either somatically recombined, as in conventional TCRs, or are already prejoined in the germ-line DNA in a manner consistent with their creation by retrotransposition. TCR does not have a known homolog in eutherian mammals but has features analogous to a recently described TCR␦ isoform in sharks. TCR is expressed in at least two mRNA isoforms that appear capable of encoding a full-length protein, both of which are transcribed in the thymus and spleen. One contains two variable domains: a somatically recombined V and a prejoined V. This appears to be the dominant isoform in peripheral lymphoid tissue. The other isoform contains only the prejoined V and is structurally more similar to conventional TCR chains, however invariant. Unlike other TCRs, TCR uses prejoined gene segments and is likely present in all marsupials. Its similarity to a TCR isoform in sharks suggests that it, or something similar, may be present in other vertebrate lineages and, therefore, may represent an ancient receptor system. evolution ͉ immune system H allmarks of the adaptive immune systems in jawed vertebrates are cells (lymphocytes) that use somatic DNA recombination to assemble the genes that encode antigen receptors. This recombination provides the means to generate a large repertoire of receptors with diverse binding specificities (1). There are two classes of antigen receptors that are used by B and T cells, respectively: Ig and T cell receptor (TCR). Although there is variation in the isotypes of Ig present, to date, all jawed vertebrates appear to have the same four TCR homologs (2, 3): TCR␣, -␤, -␥, and -␦. All contain V domains that are encoded by the variable (V), diversity (D), and joining (J) gene segments; recombined V and J encode the V domain in TCR␣ and TCR␥, whereas the TCR␤ and TCR␦ chains use V, D, and J (4). A typical TCR locus is organized in a ''translocon'' arrangement in which an array of V segments is upstream of one or more D segments (in the case of TCR␤ and TCR␦), followed by one or more J segments (4). In developing T cells, these gene segments undergo so-called VDJ recombination that is mediated, in part, by the recombination activating gene (RAG) recombinase system to assemble the exon encoding the V domain (1, 5). To date, the V, D, and J gene segments in TCR loci have always been found in a nonrecombined state in the germ-line DNA and require somatic cell recombination for expression. After recombination, T cells are then selected in the thymus to eliminate those that bind self-antigens (contributing to self-tolerance) and, in the case of ␣␤TC...

Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences

“…The opossum genome also contains a new T-cell receptor isotype that is expressed early in ontogeny, before conventional T-cell receptors, and may provide early immune function in the altricial young 37 .…”

“…Extensions to these findings, as well as additional topics, are reported in a series of companion papers [31][32][33][34][35][36][37][38][39][40][41] .…”

Evidence for a transposition event in a second NITR gene cluster in zebrafish

“…Evidence for the retrotransposition of mature mRNAs to generate new genes (or pseudogenes) has been described for more than 25 years (Lemischka and Sharp 1982) and includes a unique T cell receptor in marsupials (Parra et al 2007). Although zebrafish nitr13/nitr14 may share a common ancestry with the catfish IpNITR13/IpNITR15 genes (see above), no genomic sequence information is available for these catfish genes barring any conclusion about a retrotransposition event in catfish NITRs.…”

Physical Mapping of Immune Genes in the Tammar Wallaby <i>(Macropus eugenii)</i>

“…The ␤ chain mapped to chromosome 8q, and the ␥ chain mapped to chromosome 6q [Deakin et al, 2006b]. More recently, a TCR unique to marsupials (designated encoded by TCRM ) has been isolated and mapped to chromosome 3 in the opossum [Parra et al, 2007].…”

“…Although TCR and Ig genes have previously been isolated in the tammar wallaby [Zuccolotto et al, 2000;Harrison et al, 2003;Parra et al, 2006Parra et al, , 2007Daly et al, 2007], their location within the tammar wallaby genome is unknown. Here we have isolated tammar wallaby bacterial artificial chromosomes (BACs) containing TCR genes, TRA @ /TRD @ , TRB @ , TRG @ and TCRM and BACs containing the Ig heavy chain gene ( IGH @ ) and light chain genes ( IGL @ and IGK @ ) and physically mapped these to chromosomes in the tammar wallaby.…”