Developmentally Regulated Expression of the Transmembrane Adaptor Protein TRIM in Fetal and Adult T Cells

Abstract

TRIM is a recently identified transmembrane adaptor protein which is exclusively expressed in T cells and natural killer (NK) cells. In peripheral blood T cells TRIM has been reported to coprecipitate, comodulate, and cocap with the T‐cell receptor (TCR), suggesting that it is an integral component of the TCR/CD3/ζ complex. Here we investigate the expression of TRIM mRNAs and proteins in developing thymocytes. Two splicing isoforms with open reading frames are observed, namely a full length (TRIM) and a truncated version (ΔTM‐TRIM). The latter lacks the extracellular and transmembrane domains as well as the first 10 cytoplasmic aminoacids and is significantly expressed only as mRNA in early fetal thymocytes. TRIM mRNA is detected in all mainstream thymocyte subsets in adult mice. TRIM protein, in contrast, first appears in the DN2 (CD44+ CD25+) subset of adult double negative (DN) cells. In fetal thymocyte development, TRIM mRNA is seen from dg 14.5 onwards whereas TRIM protein appears first on dg 16.5. In contrast to the adult, the TRIM protein was seen in a subset of fetal DN1 cells. In fetal and adult thymocytes, TRIM protein expression was highest in DN2, DN3 (CD44−25+) and in DP cells, compatible with a functional role at or around phases of thymic selection.

Stoichiometry and intracellular fate of TRIM-containing TCR complexes

“…The larger αβTCR complex, that most likely includes TRIM, was present in primary cells. This is in line with our earlier data showing that TRIM co-caps with CD3 in primary human cells [18] and that TRIM is expressed in murine thymocytes [30]. …”

“…The small human γδTCR complex has a stoichiometry of TCRγδ CD3ε 2 γδζ 2 [2,28]; the larger complex likely has a TCRγδ CD3ε 2 γδζ 2 TRIM 2 stoichiometry. At the double negative stage of T cell development, TRIM is already expressed together with the pre-TCR [30], which also includes ζ. Therefore, it is likely that TRIM also associates with the pre-TCR complex.…”

Normal T-Cell Development and Immune Functions in TRIM-Deficient Mice

“…We have previously reported that TRIM is exclusively expressed in lymphoid organs (thymus, lymph node, and spleen) (4,19). As shown in Fig.…”

Transmembrane adapters: attractants for cytoplasmic effectors

“…Northern blot analysis revealed a strong expression of TRIM mRNA in thymus and to a lesser extent in spleen, lymph nodes, and peripheral blood lymphocytes (78). Also, other minor T‐cell subsets, such as γδ T lymphocytes and NK1.1 + αβ thymic T cells, express TRIM (81). A recent analysis of TRIM expression during thymic development further revealed that both TRIM mRNA and protein are expressed in the very early developmental stages (DN1‐DN2 and DN2, respectively) even before pre‐TCR assembly and signaling capacity are carried out (81).…”

“…Also, other minor T‐cell subsets, such as γδ T lymphocytes and NK1.1 + αβ thymic T cells, express TRIM (81). A recent analysis of TRIM expression during thymic development further revealed that both TRIM mRNA and protein are expressed in the very early developmental stages (DN1‐DN2 and DN2, respectively) even before pre‐TCR assembly and signaling capacity are carried out (81). In contrast, TRIM mRNA is not detectable in fetal liver or bone marrow and the protein is absent from B lymphocytes, B cell lines, the erythroleukemic cell line K562 or the monocytic cell line U937 (78).…”