TCR-Associated ζ-FcϵRlγ heterodimers on CD4−CD8− NK1.1+ t cells selected by specific class I MHC antigen

Abstract

The origin of autoreactive CD4-CD8- T cells is largely unknown. In TCR transgenic (Tg) mice expressing the cognate class I MHC antigen, CD4-CD8- T cells differed depending on characteristics of Tg-TCR/antigen interaction. Tg-TCR/CD3lo CD4-CD8- T cells expressing the NK1.1 marker were observed only for a Tg-TCR whose stimulation by antigen was independent of CD8. Unlike normal T cells, which have essentially TCR-associated zeta homodimers, these cells had a high proportion of TCR-associated zeta-Fc epsilon RI gamma heterodimers. They were also characterized by an unusually high content of Fc epsilon RI gamma mRNA and low content of mRNA encoding CD3 epsilon, CD3 gamma, CD3 delta, and zeta. Based on their phenotype and selection requirements, it is proposed that CD4-CD8- thymic precursor cells can be driven along the CD4-CD8-NK1.1+ pathway following coreceptor-independent TCR signaling at an intrathymic stage when Fc epsilon RI gamma and CD3 components are coexpressed.

Immediate antigen‐specific effector functions byTCR‐transgenic CD8+ NKT cells

“…Therefore, we consider the NK1.1-positive population of T cells we found in TCR-transgenic animals as a genuine NKT cell population. In line with such an interpretation, other groups have reported the presence of NKT cells in CD8 + TCR-transgenic mouse lines H-Y [36,37], BM3.3 [38,39] and 2C [40], as well as in the CD4 + TCR-transgenic mouse lines DO11.10 [41] and 3BBM74 [42]. Here, we extend the list of mouse lines bearing tgNKT cells to include OT-I and P14 (Fig.…”

“…However, the mice analyzed in this study were unprimed and therefore have to be considered as antigen naive. Nonetheless, NK1.1 surface expression is probably not due to a general upregulation of NK1.1 on activated CD8 + T cells, as we never detected increased NK1.1 expression on transgenic CD8 + T cells after challenge with virally encoded antigen (ovalbumin-expressing adenovirus for OT-I) or soluble antigen (OVA 257-264 for OT-I and gp33 [33][34][35][36][37][38][39][40][41] for P14) in vitro or in vivo (data not shown). Schüler et al recently reported that thymic emigrants in neonates give rise to natural memory T cells with an activated phenotype [32], although the authors did not analyze the expression of NK1.1 on these cells.…”

“…For antigen-specific stimulation, we incubated OT-I and P14 lymphocytes in vitro with OVA 257-264 or gp33 [33][34][35][36][37][38][39][40][41] peptide, respectively. In contrast to the stimulation with anti-CD3e Ab in vivo, cytokine production (IFN-c, TNF-a and IL-2) was slower and was only seen after 1.5 h of incubation.…”

Development of T cells expressing an altered TCR complex

“…T cells bearing alternative TCR complexes along with other structures are also present in mice, which contain the Fc 4 R + chain (FcR + ) and form FcR + -FcR + homodimers or FcR + -´heterodimers rather thań´h omodimers [3][4][5]. In normal mice, alternative TCR complexes are expressed on some unique population of T cells [6][7][8]. Interestingly, expression of TCR § g chains at early stages during thymocyte development can result in expression of alternative rather than conventional TCR complexes on T cells [9].…”

“…In addition, T cells from some autoimmune disease patients also express alternative TCR complexes [10]. The alternative TCR complexes are generally expressed at lower levels on those T cells than are conventional TCR complexes expressed on other T cells [6,8].…”