TCR mu Recombination and Transcription Relative to the Conventional TCR during Postnatal Development in Opossums

Marsupials are a distinct lineage of mammals notable for giving birth to highly altricial (relatively less developed) young. The recent discovery of a unique TCR chain in marsupials, TCR mu, raises questions about its possible role in early development. Here we compare the timing of V(D)J recombination and appearance of TCR mu transcripts relative to the conventional TCR alpha, beta, gamma, and delta mRNA during postnatal development in the opossum. There are two TCR mu transcript isoforms, TCR mu 1.0 and TCR mu 2.0. TCR mu 1.0, which uses prejoined V(D)J segments, is detectable as early as day 1, when the thymus is primarily undifferentiated epithelium. The other isoform, TCR mu 2.0, which requires V(D)J recombination and contains an unusual double V configuration, is not detectable until day 13 when the thymus is histologically mature. Surprisingly, we were able to detect TCR alpha, beta, and delta mRNA transcribed from loci that had completed V(D)J recombination as early as day 1 as well. At this early age there is apparent evidence for preference in the V segments used in the TCRa and 13 genes. In the case of V alpha this preference appears to be associated with position in the TCR alpha/delta locus. In V beta, however, preference may be due to the use of microhomology in the V, D, and J segments. Mature TCR gamma transcripts were not detected until day 8, suggesting that, in contrast to eutherian mammals, in the opossum alpha beta T cell development precedes gamma delta T cell development. The results support that there may be differences in T cell subset development between marsupials and placental mammals. The Journal of Immunology, 2009, 182: 154-163.