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T cells compete for access to antigen-bearing antigen-presenting cells.

Kedl RM, Rees WA, Hildeman DA, Schaefer B, Mitchell T, Kappler J, Marrack P - J. Exp. Med. (2000)

Bottom Line: OT1 cells also inhibited CD8(+) T cell responses to an unrelated peptide, SIYRYGGL, providing it was presented on the same dendritic cells as ova8.Rather, the inhibition was caused by competition for antigen and antigen-bearing cells, since it could be overcome by the injection of large numbers of antigen-pulsed dendritic cells.These results imply that common properties of T cell responses, such as epitope dominance and secondary response affinity maturation, are the result of competitive interactions between antigen-bearing APC and T cell subsets.

View Article: PubMed Central - PubMed

Affiliation: Cancer Research Institute, National Jewish Medical and Research Center Denver, Colorado 80206, USA. kedlr@njc.org

ABSTRACT
These studies tested whether antigenic competition between T cells occurs. We generated CD8(+) T cell responses in H-2(b) mice against the dominant ovalbumin epitope SIINFEKL (ova8) and subdominant epitope KRVVFDKL, using either vaccinia virus expressing ovalbumin (VV-ova) or peptide-pulsed dendritic cells. CD8(+) T cell responses were visualized by major histocompatibility complex class I-peptide tetrameric molecules. Transfer of transgenic T cells with high affinity for ova8 (OT1 T cells) completely inhibited the response of host antigen-specific T cells to either antigen, demonstrating that T cells can directly compete with each other for response to antigen. OT1 cells also inhibited CD8(+) T cell responses to an unrelated peptide, SIYRYGGL, providing it was presented on the same dendritic cells as ova8. These inhibitions were not due to a more rapid clearance of virus or antigen-presenting cells (APCs) by the OT1 cells. Rather, the inhibition was caused by competition for antigen and antigen-bearing cells, since it could be overcome by the injection of large numbers of antigen-pulsed dendritic cells. These results imply that common properties of T cell responses, such as epitope dominance and secondary response affinity maturation, are the result of competitive interactions between antigen-bearing APC and T cell subsets.

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Transferred OT1 cells compete against the secondary response of endogenous Kb/ova8-specific CD8+ T cells and inhibit affinity maturation. 25 d after initial VV-ova immunization, B6.PL mice were transferred with 3 × 106 OT1 T cells and rechallenged with VV-ova. This response was compared with that of B6.PL mice given a secondary VV-ova immunization without OT1 T cell transfer. The data were analyzed as described in the legend to Fig. 2. The numbers above the markers in the histograms are the mean fluorescence intensity of the tetramer-staining cells. The data presented are representative of three separate experiments.
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Figure 4: Transferred OT1 cells compete against the secondary response of endogenous Kb/ova8-specific CD8+ T cells and inhibit affinity maturation. 25 d after initial VV-ova immunization, B6.PL mice were transferred with 3 × 106 OT1 T cells and rechallenged with VV-ova. This response was compared with that of B6.PL mice given a secondary VV-ova immunization without OT1 T cell transfer. The data were analyzed as described in the legend to Fig. 2. The numbers above the markers in the histograms are the mean fluorescence intensity of the tetramer-staining cells. The data presented are representative of three separate experiments.

Mentions: We next tested whether transferred OT1 cells could inhibit the response of primed T cells. B6.PL mice were challenged with VV-ova and 25 d later were rechallenged with the same virus with or without transfer of OT1 transgenic T cells. The number of transferred cells was selected such that they would be in approximately the same numbers in the recipient as the endogenous Kb/ova8-specific memory cells (∼0.25% of all CD8+ T cells; data not shown). Nontransferred mice demonstrated significant expansion and affinity maturation of the endogenous T cell population after secondary challenge. However, the expansion and affinity maturation of the established endogenous memory T cells were strongly inhibited by the transferred cells (Fig. 4). Given the high affinity of the OT1 TCR for antigen (1–6 μM), these data suggest that the affinity of a given T cell enhances its ability to compete for access to, and expansion from, antigen stimulation. It should be noted that the low level of tetramer staining of the OT1 cells after activation is due primarily to a high degree of receptor downregulation (see Discussion).


T cells compete for access to antigen-bearing antigen-presenting cells.

Kedl RM, Rees WA, Hildeman DA, Schaefer B, Mitchell T, Kappler J, Marrack P - J. Exp. Med. (2000)

Transferred OT1 cells compete against the secondary response of endogenous Kb/ova8-specific CD8+ T cells and inhibit affinity maturation. 25 d after initial VV-ova immunization, B6.PL mice were transferred with 3 × 106 OT1 T cells and rechallenged with VV-ova. This response was compared with that of B6.PL mice given a secondary VV-ova immunization without OT1 T cell transfer. The data were analyzed as described in the legend to Fig. 2. The numbers above the markers in the histograms are the mean fluorescence intensity of the tetramer-staining cells. The data presented are representative of three separate experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2195874&req=5

Figure 4: Transferred OT1 cells compete against the secondary response of endogenous Kb/ova8-specific CD8+ T cells and inhibit affinity maturation. 25 d after initial VV-ova immunization, B6.PL mice were transferred with 3 × 106 OT1 T cells and rechallenged with VV-ova. This response was compared with that of B6.PL mice given a secondary VV-ova immunization without OT1 T cell transfer. The data were analyzed as described in the legend to Fig. 2. The numbers above the markers in the histograms are the mean fluorescence intensity of the tetramer-staining cells. The data presented are representative of three separate experiments.
Mentions: We next tested whether transferred OT1 cells could inhibit the response of primed T cells. B6.PL mice were challenged with VV-ova and 25 d later were rechallenged with the same virus with or without transfer of OT1 transgenic T cells. The number of transferred cells was selected such that they would be in approximately the same numbers in the recipient as the endogenous Kb/ova8-specific memory cells (∼0.25% of all CD8+ T cells; data not shown). Nontransferred mice demonstrated significant expansion and affinity maturation of the endogenous T cell population after secondary challenge. However, the expansion and affinity maturation of the established endogenous memory T cells were strongly inhibited by the transferred cells (Fig. 4). Given the high affinity of the OT1 TCR for antigen (1–6 μM), these data suggest that the affinity of a given T cell enhances its ability to compete for access to, and expansion from, antigen stimulation. It should be noted that the low level of tetramer staining of the OT1 cells after activation is due primarily to a high degree of receptor downregulation (see Discussion).

Bottom Line: OT1 cells also inhibited CD8(+) T cell responses to an unrelated peptide, SIYRYGGL, providing it was presented on the same dendritic cells as ova8.Rather, the inhibition was caused by competition for antigen and antigen-bearing cells, since it could be overcome by the injection of large numbers of antigen-pulsed dendritic cells.These results imply that common properties of T cell responses, such as epitope dominance and secondary response affinity maturation, are the result of competitive interactions between antigen-bearing APC and T cell subsets.

View Article: PubMed Central - PubMed

Affiliation: Cancer Research Institute, National Jewish Medical and Research Center Denver, Colorado 80206, USA. kedlr@njc.org

ABSTRACT
These studies tested whether antigenic competition between T cells occurs. We generated CD8(+) T cell responses in H-2(b) mice against the dominant ovalbumin epitope SIINFEKL (ova8) and subdominant epitope KRVVFDKL, using either vaccinia virus expressing ovalbumin (VV-ova) or peptide-pulsed dendritic cells. CD8(+) T cell responses were visualized by major histocompatibility complex class I-peptide tetrameric molecules. Transfer of transgenic T cells with high affinity for ova8 (OT1 T cells) completely inhibited the response of host antigen-specific T cells to either antigen, demonstrating that T cells can directly compete with each other for response to antigen. OT1 cells also inhibited CD8(+) T cell responses to an unrelated peptide, SIYRYGGL, providing it was presented on the same dendritic cells as ova8. These inhibitions were not due to a more rapid clearance of virus or antigen-presenting cells (APCs) by the OT1 cells. Rather, the inhibition was caused by competition for antigen and antigen-bearing cells, since it could be overcome by the injection of large numbers of antigen-pulsed dendritic cells. These results imply that common properties of T cell responses, such as epitope dominance and secondary response affinity maturation, are the result of competitive interactions between antigen-bearing APC and T cell subsets.

Show MeSH
Related in: MedlinePlus