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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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Downregulation of coreceptors can occur in the absence of  an interaction with cognate or noncognate MHC molecules. Downregulation of CD3 and coreceptor in CD4+ (KS70; A) or CD8+ (CER43; B)  T cell clones stimulated by specific peptide–MHC (•), superantigens  (□), or monovalent anti-CD3 antibodies: w632/T3 (▵), L243/T3 (○).  (C) Downregulation of CD3 versus CD4 (▴) and CD8 (○) in alloreactive CD4+ CD8+ T cell clones stimulated by specific alloantigen (D).  Downregulation of CD3 and CD8 in CD8+, class II–alloreactive T cell  clones stimulated with class I− APCs (.221) expressing the relevant class II  alloantigen.
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Figure 2: Downregulation of coreceptors can occur in the absence of an interaction with cognate or noncognate MHC molecules. Downregulation of CD3 and coreceptor in CD4+ (KS70; A) or CD8+ (CER43; B) T cell clones stimulated by specific peptide–MHC (•), superantigens (□), or monovalent anti-CD3 antibodies: w632/T3 (▵), L243/T3 (○). (C) Downregulation of CD3 versus CD4 (▴) and CD8 (○) in alloreactive CD4+ CD8+ T cell clones stimulated by specific alloantigen (D). Downregulation of CD3 and CD8 in CD8+, class II–alloreactive T cell clones stimulated with class I− APCs (.221) expressing the relevant class II alloantigen.

Mentions: We investigated whether the codownregulation of TCR and coreceptor would require the interaction between coreceptor and cognate MHC molecule or whether it would simply be a consequence of TCR triggering. Three lines of evidence indicate that coreceptor downregulation can occur in the absence of interaction with the cognate MHC molecule. First, a parallel downregulation of TCR and coreceptor was induced not only by specific peptide–MHC complexes, but also by bacterial superantigens or monovalent anti-CD3 antibodies (Fig. 2, A and B). Second, class I–restricted T cell clones expressing both CD4 and CD8 downregulated both coreceptors to the same extent (Fig. 2 C). Third, class II–alloreactive CD8+ T cell clones, when stimulated by class II+ APCs lacking class I molecules, downregulated CD8 together with TCR (Fig. 2 D).


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)

Downregulation of coreceptors can occur in the absence of  an interaction with cognate or noncognate MHC molecules. Downregulation of CD3 and coreceptor in CD4+ (KS70; A) or CD8+ (CER43; B)  T cell clones stimulated by specific peptide–MHC (•), superantigens  (□), or monovalent anti-CD3 antibodies: w632/T3 (▵), L243/T3 (○).  (C) Downregulation of CD3 versus CD4 (▴) and CD8 (○) in alloreactive CD4+ CD8+ T cell clones stimulated by specific alloantigen (D).  Downregulation of CD3 and CD8 in CD8+, class II–alloreactive T cell  clones stimulated with class I− APCs (.221) expressing the relevant class II  alloantigen.
© Copyright Policy
Related In: Results  -  Collection

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Figure 2: Downregulation of coreceptors can occur in the absence of an interaction with cognate or noncognate MHC molecules. Downregulation of CD3 and coreceptor in CD4+ (KS70; A) or CD8+ (CER43; B) T cell clones stimulated by specific peptide–MHC (•), superantigens (□), or monovalent anti-CD3 antibodies: w632/T3 (▵), L243/T3 (○). (C) Downregulation of CD3 versus CD4 (▴) and CD8 (○) in alloreactive CD4+ CD8+ T cell clones stimulated by specific alloantigen (D). Downregulation of CD3 and CD8 in CD8+, class II–alloreactive T cell clones stimulated with class I− APCs (.221) expressing the relevant class II alloantigen.
Mentions: We investigated whether the codownregulation of TCR and coreceptor would require the interaction between coreceptor and cognate MHC molecule or whether it would simply be a consequence of TCR triggering. Three lines of evidence indicate that coreceptor downregulation can occur in the absence of interaction with the cognate MHC molecule. First, a parallel downregulation of TCR and coreceptor was induced not only by specific peptide–MHC complexes, but also by bacterial superantigens or monovalent anti-CD3 antibodies (Fig. 2, A and B). Second, class I–restricted T cell clones expressing both CD4 and CD8 downregulated both coreceptors to the same extent (Fig. 2 C). Third, class II–alloreactive CD8+ T cell clones, when stimulated by class II+ APCs lacking class I molecules, downregulated CD8 together with TCR (Fig. 2 D).

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