Limits...
Role of the multiple T cell receptor (TCR)-zeta chain signaling motifs in selection of the T cell repertoire.

Shores EW, Tran T, Grinberg A, Sommers CL, Shen H, Love PE - J. Exp. Med. (1997)

Bottom Line: The TCR is composed of four distinct signal transducing subunits (CD3-gamma, -delta, -epsilon, and zeta) that contain either one (CD3-gamma, -delta, -epsilon) or three (-zeta) signaling motifs (ITAMs) within their intracytoplasmic domains.A possible function for multiple TCR ITAMs could be to amplify signals generated by the TCR during selection.A direct relationship was observed between the number of zeta chain ITAMs within the TCR complex and the efficiency of both positive and negative selection.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematologic Products, Food and Drug Administration, Bethesda, Maryland 20892, USA.

ABSTRACT
Immature thymocytes undergo a selection process within the thymus based on their T cell antigen receptor (TCR) specificity that results either in their maturation into functionally competent, self-MHC-restricted T cells (positive selection) or their deletion (negative selection). The outcome of thymocyte selection is thought to be controlled by signals transduced by the TCR that vary in relation to the avidity of the TCR-ligand interaction. The TCR is composed of four distinct signal transducing subunits (CD3-gamma, -delta, -epsilon, and zeta) that contain either one (CD3-gamma, -delta, -epsilon) or three (-zeta) signaling motifs (ITAMs) within their intracytoplasmic domains. A possible function for multiple TCR ITAMs could be to amplify signals generated by the TCR during selection. To determine the importance of the multiple TCR-zeta chain ITAMs in thymocyte selection, transgenes encoding alpha/beta TCRs with known specificity were bred into mice in which zeta chains lacking one or more ITAMs had been genetically substituted for endogenous zeta. A direct relationship was observed between the number of zeta chain ITAMs within the TCR complex and the efficiency of both positive and negative selection. These results reveal a role for multiple TCR ITAMs in thymocyte selection and identify a function for TCR signal amplification in formation of the T cell repertoire.

Show MeSH
Role of TCR-ζ chain ITAMs in mature T cell function. (A)  Proliferative response of LN T cells to anti-CD3ε and Con A stimulation.  (B) Proliferative response of LN T cells to allogenic stimulator cells. LN  T cells were obtained from 4–8-wk-old nontransgenic (ζ+/+/) mice, or  ζ−/− mice that express transgenes encoding either full-length ζ chain (ζ-3  ITAM Tg) or ζ chain lacking ITAM sequences (ζ-0 ITAM Tg) and stimulated as described in Materials and Methods.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2196173&req=5

Figure 1: Role of TCR-ζ chain ITAMs in mature T cell function. (A) Proliferative response of LN T cells to anti-CD3ε and Con A stimulation. (B) Proliferative response of LN T cells to allogenic stimulator cells. LN T cells were obtained from 4–8-wk-old nontransgenic (ζ+/+/) mice, or ζ−/− mice that express transgenes encoding either full-length ζ chain (ζ-3 ITAM Tg) or ζ chain lacking ITAM sequences (ζ-0 ITAM Tg) and stimulated as described in Materials and Methods.

Mentions: Reconstitution of ζ−/− mice with a transgene encoding a ζ variant chain lacking all three ζ chain ITAMs (ζ-0 ITAM) restores TCR surface expression and promotes the generation of large numbers of CD4+CD8− and CD4−CD8+ SP thymocytes and peripheral T cells (15). Significantly, the T cells generated in ζ-0 ITAM Tg mice are functionally competent as assessed by their ability to respond to TCR-dependent stimuli (Fig. 1; 23). These results demonstrate that TCR-ζ chain signals are not specifically required for either the generation or activation of mature T cells.


Role of the multiple T cell receptor (TCR)-zeta chain signaling motifs in selection of the T cell repertoire.

Shores EW, Tran T, Grinberg A, Sommers CL, Shen H, Love PE - J. Exp. Med. (1997)

Role of TCR-ζ chain ITAMs in mature T cell function. (A)  Proliferative response of LN T cells to anti-CD3ε and Con A stimulation.  (B) Proliferative response of LN T cells to allogenic stimulator cells. LN  T cells were obtained from 4–8-wk-old nontransgenic (ζ+/+/) mice, or  ζ−/− mice that express transgenes encoding either full-length ζ chain (ζ-3  ITAM Tg) or ζ chain lacking ITAM sequences (ζ-0 ITAM Tg) and stimulated as described in Materials and Methods.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196173&req=5

Figure 1: Role of TCR-ζ chain ITAMs in mature T cell function. (A) Proliferative response of LN T cells to anti-CD3ε and Con A stimulation. (B) Proliferative response of LN T cells to allogenic stimulator cells. LN T cells were obtained from 4–8-wk-old nontransgenic (ζ+/+/) mice, or ζ−/− mice that express transgenes encoding either full-length ζ chain (ζ-3 ITAM Tg) or ζ chain lacking ITAM sequences (ζ-0 ITAM Tg) and stimulated as described in Materials and Methods.
Mentions: Reconstitution of ζ−/− mice with a transgene encoding a ζ variant chain lacking all three ζ chain ITAMs (ζ-0 ITAM) restores TCR surface expression and promotes the generation of large numbers of CD4+CD8− and CD4−CD8+ SP thymocytes and peripheral T cells (15). Significantly, the T cells generated in ζ-0 ITAM Tg mice are functionally competent as assessed by their ability to respond to TCR-dependent stimuli (Fig. 1; 23). These results demonstrate that TCR-ζ chain signals are not specifically required for either the generation or activation of mature T cells.

Bottom Line: The TCR is composed of four distinct signal transducing subunits (CD3-gamma, -delta, -epsilon, and zeta) that contain either one (CD3-gamma, -delta, -epsilon) or three (-zeta) signaling motifs (ITAMs) within their intracytoplasmic domains.A possible function for multiple TCR ITAMs could be to amplify signals generated by the TCR during selection.A direct relationship was observed between the number of zeta chain ITAMs within the TCR complex and the efficiency of both positive and negative selection.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematologic Products, Food and Drug Administration, Bethesda, Maryland 20892, USA.

ABSTRACT
Immature thymocytes undergo a selection process within the thymus based on their T cell antigen receptor (TCR) specificity that results either in their maturation into functionally competent, self-MHC-restricted T cells (positive selection) or their deletion (negative selection). The outcome of thymocyte selection is thought to be controlled by signals transduced by the TCR that vary in relation to the avidity of the TCR-ligand interaction. The TCR is composed of four distinct signal transducing subunits (CD3-gamma, -delta, -epsilon, and zeta) that contain either one (CD3-gamma, -delta, -epsilon) or three (-zeta) signaling motifs (ITAMs) within their intracytoplasmic domains. A possible function for multiple TCR ITAMs could be to amplify signals generated by the TCR during selection. To determine the importance of the multiple TCR-zeta chain ITAMs in thymocyte selection, transgenes encoding alpha/beta TCRs with known specificity were bred into mice in which zeta chains lacking one or more ITAMs had been genetically substituted for endogenous zeta. A direct relationship was observed between the number of zeta chain ITAMs within the TCR complex and the efficiency of both positive and negative selection. These results reveal a role for multiple TCR ITAMs in thymocyte selection and identify a function for TCR signal amplification in formation of the T cell repertoire.

Show MeSH