scholarly journals Effects of Epitope Modification on T Cell Receptor–Ligand Binding and Antigen Recognition by Seven H-2Kd–restricted Cytotoxic T Lymphocyte Clones Specific for a Photoreactive Peptide Derivative

1997 ◽  
Vol 185 (4) ◽  
pp. 629-640 ◽  
Author(s):  
Benedikt M. Kessler ◽  
Paolo Bassanini ◽  
Jean-Charles Cerottini ◽  
Immanuel F. Luescher
Keyword(s):  
T Cell ◽  
Ligand Binding ◽  
T Cell Receptor ◽  
Cytotoxic T Lymphocyte ◽  
Critical Role ◽  
Cell Receptor ◽  
Antigen Recognition ◽  
Chromium Release ◽  
Peptide Derivative ◽  
Binding Avidity

We tested for antigen recognition and T cell receptor (TCR)–ligand binding 12 peptide derivative variants on seven H-2Kd–restricted cytotoxic T lymphocytes (CTL) clones specific for a bifunctional photoreactive derivative of the Plasmodium berghei circumsporozoite peptide 252– 260 (SYIPSAEKI). The derivative contained iodo-4-azidosalicylic acid in place of PbCS S-252 and 4-azidobenzoic acid on PbCS K-259. Selective photoactivation of the N-terminal photoreactive group allowed crosslinking to Kd molecules and photoactivation of the orthogonal group to TCR. TCR photoaffinity labeling with covalent Kd–peptide derivative complexes allowed direct assessment of TCR–ligand binding on living CTL. In most cases (over 80%) cytotoxicity (chromium release) and TCR–ligand binding differed by less than fivefold. The exceptions included (a) partial TCR agonists (8 cases), for which antigen recognition was fivetenfold less efficient than TCR–ligand binding, (b) TCR antagonists (2 cases), which were not recognized and capable of inhibiting recognition of the wild-type conjugate, (c) heteroclitic agonists (2 cases), for which antigen recognition was more efficient than TCR–ligand binding, and (d) one partial TCR agonist, which activated only Fas (CD95), but not perforin/granzymemediated cytotoxicity. There was no correlation between these divergences and the avidity of TCR–ligand binding, indicating that other factors than binding avidity determine the nature of the CTL response. An unexpected and novel finding was that CD8-dependent clones clearly incline more to TCR antagonism than CD8-independent ones. As there was no correlation between CD8 dependence and the avidity of TCR–ligand binding, the possibility is suggested that CD8 plays a critical role in aberrant CTL function.

scholarly journals CD8β Increases CD8 Coreceptor Function and Participation in TCR–Ligand Binding

1996 ◽  
Vol 184 (6) ◽  
pp. 2439-2444 ◽  
Author(s):  
Valery Renard ◽  
Pedro Romero ◽  
Eric Vivier ◽  
Bernard Malissen ◽  
Immanuel F. Luescher
Keyword(s):  
T Cell ◽  
Ligand Binding ◽  
Cell Function ◽  
Cytotoxic T Lymphocyte ◽  
Photoaffinity Labeling ◽  
Interleukin 2 ◽  
Cell Receptor ◽  
Β Cells ◽  
Cd8 Cells ◽  
Peptide Derivative

To study the role of CD8β in T cell function, we derived a CD8α/β− (CD8−/−) T cell hybridoma of the H-2Kd–restricted N9 cytotoxic T lymphocyte clone specific for a photoreactive derivative of the Plasmodium berghei circumsporozoite peptide PbCS 252-260. This hybridoma was transfected either with CD8α alone or together with CD8β. All three hybridomas released interleukin 2 upon incubation with L cells expressing Kd–peptide derivative complexes, though CD8α/β cells did so more efficiently than CD8α/α and especially CD8−/− cells. More strikingly, only CD8α/β cells were able to recognize a weak agonist peptide derivative variant. This recognition was abolished by Fab′ fragments of the anti-Kd α3 monoclonal antibody SF11.1.1 or substitution of Kd D-227 with K, both conditions known to impair CD8 coreceptor function. T cell receptor (TCR) photoaffinity labeling indicated that TCR–ligand binding on CD8α/β cells was ∼5- and 20-fold more avid than on CD8α/a and CD8−/− cells, respectively. SF1-1.1.1 Fab′ or Kd mutation D227K reduced the TCR photoaffinity labeling on CD8α/β cells to approximately the same low levels observed on CD8−/− cells. These results indicate that CD8α/β is a more efficient coreceptor than CD8α/α, because it more avidly strengthens TCR–ligand binding.

scholarly journals CD8β Endows CD8 with Efficient Coreceptor Function by Coupling T Cell Receptor/CD3 to Raft-associated CD8/p56lck Complexes

2001 ◽  
Vol 194 (10) ◽  
pp. 1485-1495 ◽  
Author(s):  
Alexandre Arcaro ◽  
Claude Grégoire ◽  
Talitha R. Bakker ◽  
Lucia Baldi ◽  
Martin Jordan ◽  
...  
Keyword(s):  
T Cell ◽  
Ligand Binding ◽  
T Cell Receptor ◽  
T Cell Activation ◽  
Cd8 T Cells ◽  
Cell Activation ◽  
Cell Receptor ◽  
High Affinity ◽  
Histocompatibility Complex ◽  
Peptide Derivative

The extraordinary sensitivity of CD8+ T cells to recognize antigen impinges to a large extent on the coreceptor CD8. While several studies have shown that the CD8β chain endows CD8 with efficient coreceptor function, the molecular basis for this is enigmatic. Here we report that cell-associated CD8αβ, but not CD8αα or soluble CD8αβ, substantially increases the avidity of T cell receptor (TCR)-ligand binding. To elucidate how the cytoplasmic and transmembrane portions of CD8β endow CD8 with efficient coreceptor function, we examined T1.4 T cell hybridomas transfected with various CD8β constructs. T1.4 hybridomas recognize a photoreactive Plasmodium berghei circumsporozoite (PbCS) peptide derivative (PbCS (4-azidobezoic acid [ABA])) in the context of H-2Kd, and permit assessment of TCR-ligand binding by TCR photoaffinity labeling. We find that the cytoplasmic portion of CD8β, mainly due to its palmitoylation, mediates partitioning of CD8 in lipid rafts, where it efficiently associates with p56lck. In addition, the cytoplasmic portion of CD8β mediates constitutive association of CD8 with TCR/CD3. The resulting TCR-CD8 adducts exhibit high affinity for major histocompatibility complex (MHC)-peptide. Importantly, because CD8αβ partitions in rafts, its interaction with TCR/CD3 promotes raft association of TCR/CD3. Engagement of these TCR/CD3-CD8/lck adducts by multimeric MHC-peptide induces activation of p56lck in rafts, which in turn phosphorylates CD3 and initiates T cell activation.

scholarly journals Differential T cell receptor photoaffinity labeling among H-2Kd restricted cytotoxic T lymphocyte clones specific for a photoreactive peptide derivative. Labeling of the alpha-chain correlates with J alpha segment usage.

1993 ◽  
Vol 177 (5) ◽  
pp. 1247-1256 ◽  
Author(s):  
P Romero ◽  
J L Casanova ◽  
J C Cerottini ◽  
J L Maryanski ◽  
I F Luescher
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Photoaffinity Labeling ◽  
Cell Receptor ◽  
Tryptophan Residue ◽  
Alpha Chain ◽  
Peptide Derivative ◽  
Specificity Pattern

Using a direct binding assay based on photoaffinity labeling, we studied the interaction of T cell receptor (TCR) with a Kd-bound photoreactive peptide derivative on living cells. The Kd-restricted Plasmodium berghei circumsporozoite (PbCS) peptide 253-260 (YIPSAEKI) was reacted NH2-terminally with biotin and at the TCR contact residue Lys259 with photoreactive iodo, 4-azido salicylic acid (IASA) to make biotin-YIPSAEK(IASA)I. Cytotoxic T lymphocyte (CTL) clones derived from mice immunized with this derivative recognized this conjugate, but not a related one lacking the IASA group nor the parental PbCS peptide. The clones were Kd restricted. Recognition experiments with variant conjugates, lacking substituents from IASA, revealed a diverse fine specificity pattern and indicated that this group interacted directly with the TCR. The TCR of four clones could be photoaffinity labeled by biotin-YIPSAEK(125IASA)I. This labeling was dependent on the conjugates binding to the Kd molecule and was selective for the TCR alpha (2 clones) or beta chain (1 clone), or was common for both chains (1 clone). TCR sequence analysis showed a preferential usage of J alpha TA28 containing alpha chains that were paired with V beta 1 expressing beta chains. The TCR that were photoaffinity labeled at the alpha chain expressed these J alpha and V beta segments. The tryptophan encoded by the J alpha TA28 segment is rarely found in other J alpha segments. Moreover, we show that the IASA group interacts preferentially with tryptophan in aqueous solution. We thus propose that for these CTL clones, labeling of the alpha chain occurs via the J alpha-encoded tryptophan residue.

CD1d–lipid-antigen recognition by the semi-invariant NKT T-cell receptor

Nature ◽  
2007 ◽  
Vol 448 (7149) ◽  
pp. 44-49 ◽  
Author(s):  
Natalie A. Borg ◽  
Kwok S. Wun ◽  
Lars Kjer-Nielsen ◽  
Matthew C. J. Wilce ◽  
Daniel G. Pellicci ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Antigen Recognition ◽  
Lipid Antigen

scholarly journals Similarity between fluorescein-specific T-cell receptor and antibody in chemical details of antigen recognition.

1992 ◽  
Vol 89 (23) ◽  
pp. 11552-11556 ◽  
Author(s):  
R. K. Ganju ◽  
S. T. Smiley ◽  
J. Bajorath ◽  
J. Novotny ◽  
E. L. Reinherz
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Antigen Recognition

scholarly journals T cell receptor for antigen induces linker for activation of T cell–dependent activation of a negative signaling complex involving Dok-2, SHIP-1, and Grb-2

2006 ◽  
Vol 203 (11) ◽  
pp. 2509-2518 ◽  
Author(s):  
Shen Dong ◽  
Béatrice Corre ◽  
Eliane Foulon ◽  
Evelyne Dufour ◽  
André Veillette ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Critical Role ◽  
Adaptor Proteins ◽  
Cell Receptor ◽  
Negative Control ◽  
Inositol Polyphosphate ◽  
Tcr Signaling ◽  
Signaling Complex ◽  
Src Homology 2 Domain

Adaptor proteins positively or negatively regulate the T cell receptor for antigen (TCR) signaling cascade. We report that after TCR stimulation, the inhibitory adaptor downstream of kinase (Dok)-2 and its homologue Dok-1 are involved in a multimolecular complex including the lipid phosphatase Src homology 2 domain–containing inositol polyphosphate 5′-phosphatase (SHIP)-1 and Grb-2 which interacts with the membrane signaling scaffold linker for activation of T cells (LAT). Knockdown of LAT and SHIP-1 expression indicated that SHIP-1 favored recruitment of Dok-2 to LAT. Knockdown of Dok-2 and Dok-1 revealed their negative control on Akt and, unexpectedly, on Zap-70 activation. Our findings support the view that Dok-1 and -2 are critical elements of a LAT-dependent negative feedback loop that attenuates early TCR signal. Dok-1 and -2 may therefore exert a critical role in shaping the immune response and as gatekeepers for T cell tolerance.

scholarly journals Alanine Scanning Mutagenesis of an αβ T Cell Receptor: Mapping the Energy of Antigen Recognition

Immunity ◽  
1998 ◽  
Vol 8 (4) ◽  
pp. 413-425 ◽  
Author(s):  
Thomas C Manning ◽  
Carol J Schlueter ◽  
Thomas C Brodnicki ◽  
Evan A Parke ◽  
Jeffrey A Speir ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Antigen Recognition ◽  
Alanine Scanning Mutagenesis ◽  
Alanine Scanning ◽  
Receptor Mapping
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