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Quantitative contribution of CD4 and CD8 to T cell antigen receptor serial triggering.

Viola A, Salio M, Tuosto L, Linkert S, Acuto O, Lanzavecchia A - J. Exp. Med. (1997)

Bottom Line: This coordinated disappearance takes place whenever the TCR is triggered, even when the coreceptor does not engage the cognate MHC molecule and is the consequence of binding of the coreceptor-associated Lck to ZAP-70.The interaction of coreceptor and cognate MHC molecules is dispensable when T cells are stimulated by optimal ligands, but becomes crucial when suboptimal ligands are used.In the latter case the coreceptor increases the efficiency of TCR triggering without changing the activation threshold or the quality of the T cell response.

View Article: PubMed Central - PubMed

Affiliation: Basel Institute for Immunology, Switzerland. viola@bii.ch

ABSTRACT
CD4 and CD8 are thought to function as coreceptors by binding to the cognate major histocompatibility complex (MHC) molecules recognized by the T cell antigen receptor (TCR) and initiating the signal transduction cascade. We report that during T cell-antigen-presenting cell interaction, triggered TCRs and coreceptors are downregulated and degraded with identical kinetics. This coordinated disappearance takes place whenever the TCR is triggered, even when the coreceptor does not engage the cognate MHC molecule and is the consequence of binding of the coreceptor-associated Lck to ZAP-70. The interaction of coreceptor and cognate MHC molecules is dispensable when T cells are stimulated by optimal ligands, but becomes crucial when suboptimal ligands are used. In the latter case the coreceptor increases the efficiency of TCR triggering without changing the activation threshold or the quality of the T cell response.

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Related in: MedlinePlus

The sensitivity to  inhibition by anti-CD4 depends  on the nature of the ligand. (A  and B) Proliferative response of  clone KS70 to various doses of  TSST or TT830-843 in the  presence (▴) or absence (▵) of  anti-CD4. (C) Proliferative response of clone KS164 to  TT830-843 (•, ○) or to  TT830-843 Ala839-substituted  peptide that behaves as a weak  agonist (▪, □) in the presence  (•, ▪) or absence (○, □) of  anti-CD4.
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Figure 4: The sensitivity to inhibition by anti-CD4 depends on the nature of the ligand. (A and B) Proliferative response of clone KS70 to various doses of TSST or TT830-843 in the presence (▴) or absence (▵) of anti-CD4. (C) Proliferative response of clone KS164 to TT830-843 (•, ○) or to TT830-843 Ala839-substituted peptide that behaves as a weak agonist (▪, □) in the presence (•, ▪) or absence (○, □) of anti-CD4.

Mentions: To address this point, we stimulated T cell clones with ligands of different potency and tested the effect of CD4 or CD8 antibodies on the extent of TCR triggering, the T cell activation threshold, and the quality of the response. As shown in Fig. 4, the proliferative response of T cell clone KS70 was not affected by anti-CD4 antibody when the clone was triggered by the bacterial superantigen TSST, but was inhibited by anti-CD4 when the clone was triggered by peptide–MHC complexes. Interestingly, clone KS164, which displayed a better dose–response curve to the same peptide–DR complex, was not inhibited by anti-CD4. However, this clone became sensitive to inhibition when a modified peptide with weaker agonistic properties was used. Comparable results were obtained with two additional CD4+ and two additional CD8+ clones, indicating that the sensitivity to inhibition by anticoreceptor antibodies is inversely correlated to the efficiency of the TCR–ligand interaction.


Quantitative contribution of CD4 and CD8 to T cell antigen receptor serial triggering.

Viola A, Salio M, Tuosto L, Linkert S, Acuto O, Lanzavecchia A - J. Exp. Med. (1997)

The sensitivity to  inhibition by anti-CD4 depends  on the nature of the ligand. (A  and B) Proliferative response of  clone KS70 to various doses of  TSST or TT830-843 in the  presence (▴) or absence (▵) of  anti-CD4. (C) Proliferative response of clone KS164 to  TT830-843 (•, ○) or to  TT830-843 Ala839-substituted  peptide that behaves as a weak  agonist (▪, □) in the presence  (•, ▪) or absence (○, □) of  anti-CD4.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199127&req=5

Figure 4: The sensitivity to inhibition by anti-CD4 depends on the nature of the ligand. (A and B) Proliferative response of clone KS70 to various doses of TSST or TT830-843 in the presence (▴) or absence (▵) of anti-CD4. (C) Proliferative response of clone KS164 to TT830-843 (•, ○) or to TT830-843 Ala839-substituted peptide that behaves as a weak agonist (▪, □) in the presence (•, ▪) or absence (○, □) of anti-CD4.
Mentions: To address this point, we stimulated T cell clones with ligands of different potency and tested the effect of CD4 or CD8 antibodies on the extent of TCR triggering, the T cell activation threshold, and the quality of the response. As shown in Fig. 4, the proliferative response of T cell clone KS70 was not affected by anti-CD4 antibody when the clone was triggered by the bacterial superantigen TSST, but was inhibited by anti-CD4 when the clone was triggered by peptide–MHC complexes. Interestingly, clone KS164, which displayed a better dose–response curve to the same peptide–DR complex, was not inhibited by anti-CD4. However, this clone became sensitive to inhibition when a modified peptide with weaker agonistic properties was used. Comparable results were obtained with two additional CD4+ and two additional CD8+ clones, indicating that the sensitivity to inhibition by anticoreceptor antibodies is inversely correlated to the efficiency of the TCR–ligand interaction.

Bottom Line: This coordinated disappearance takes place whenever the TCR is triggered, even when the coreceptor does not engage the cognate MHC molecule and is the consequence of binding of the coreceptor-associated Lck to ZAP-70.The interaction of coreceptor and cognate MHC molecules is dispensable when T cells are stimulated by optimal ligands, but becomes crucial when suboptimal ligands are used.In the latter case the coreceptor increases the efficiency of TCR triggering without changing the activation threshold or the quality of the T cell response.

View Article: PubMed Central - PubMed

Affiliation: Basel Institute for Immunology, Switzerland. viola@bii.ch

ABSTRACT
CD4 and CD8 are thought to function as coreceptors by binding to the cognate major histocompatibility complex (MHC) molecules recognized by the T cell antigen receptor (TCR) and initiating the signal transduction cascade. We report that during T cell-antigen-presenting cell interaction, triggered TCRs and coreceptors are downregulated and degraded with identical kinetics. This coordinated disappearance takes place whenever the TCR is triggered, even when the coreceptor does not engage the cognate MHC molecule and is the consequence of binding of the coreceptor-associated Lck to ZAP-70. The interaction of coreceptor and cognate MHC molecules is dispensable when T cells are stimulated by optimal ligands, but becomes crucial when suboptimal ligands are used. In the latter case the coreceptor increases the efficiency of TCR triggering without changing the activation threshold or the quality of the T cell response.

Show MeSH
Related in: MedlinePlus