scholarly journals Mobilization of pre-existing polyclonal T cells specific to neoantigens but not self-antigens during treatment of a patient with melanoma with bempegaldesleukin and nivolumab

2020 ◽  
Vol 8 (2) ◽  
pp. e001591
Author(s):  
Joshua R Veatch ◽  
Naina Singhi ◽  
Brenda Jesernig ◽  
Kelly G Paulson ◽  
Jonathan Zalevsky ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Interleukin 2 ◽  
Interferon Γ ◽  
Immune Checkpoint Blockade ◽  
Tumor Rejection ◽  
T Cell Clones ◽  
Cell Clones ◽  
Self Antigen ◽  
Self Antigens

T cells that recognize self-antigens and mutated neoantigens are thought to mediate antitumor activity of immune checkpoint blockade (ICB) in melanoma. Few studies have analyzed self and neoantigen-specific T cell responses in patients responding to ICB. Here, we report a patient with metastatic melanoma who had a durable clinical response after treatment with the programmed cell death protein 1 inhibitor, nivolumab, combined with the first-in-class CD122-preferential interleukin-2 pathway agonist, bempegaldesleukin (BEMPEG, NKTR-214). We used a combination of antigen-specific T cell expansion and measurement of interferon-γ secretion to identify multiple CD4+ and CD8+ T cell clones specific for neoantigens, lineage-specific antigens and cancer testis antigens in blood and tumor from this patient prior to and after therapy. Polyclonal CD4+ and CD8+ T cells specific to multiple neoantigens but not self-antigens were highly enriched in pretreatment tumor compared with peripheral blood. Neoantigen, but not self-antigen-specific T cell clones expanded in frequency in the blood during successful treatment. There was evidence of dramatic immune infiltration into the tumor on treatment, and a modest increase in the relative frequency of intratumoral neoantigen-specific T cells. These observations suggest that diverse CD8+ and CD4+ T cell clones specific for neoantigens present in tumor before treatment had a greater role in immune tumor rejection as compared with self-antigen-specific T cells in this patient. Trial registration number: NCT02983045.

Diminished Production of Interleukin 2 and Gamma-Interferon by Cloned «T» Cells from Patients with the Acquired Immunodeficiency Syndrome (AIDS)

1987 ◽  
Vol 73 (3) ◽  
pp. 273-278 ◽  
Author(s):  
Enrico Maggi ◽  
Donatella Macchia ◽  
Paola Parronchi ◽  
Domenico Milo ◽  
Sergio Romagnani
Keyword(s):  
T Cells ◽  
T Cell ◽  
Interleukin 2 ◽  
Immune Deficiency Syndrome ◽  
Gamma Interferon ◽  
Aids Patients ◽  
T Cell Clones ◽  
Cell Clones ◽  
The Mean ◽  
Mean Concentration

A total of 76 T-cell clones established from peripheral blood (PB) of 2 patients with the acquired immune deficiency syndrome (AIDS) and of 141 T-cell clones established from PB of 3 normal donors were compared for their ability to produce interleukin 2 (IL-2) and gamma-interferon (γ-IFN). Twenty-seven clones from AIDS patients and 85 clones from controls expressed the CD4 phenotype, whereas 49 clones from AIDS patients and 56 clones from controls expressed the CD8 phenotype. There were no significant differences in the proportions of IL-2-producing CD4 T-cell clones established from PB of patients with AIDS and controls, but the mean concentration of IL-2 produced by CD4 clones from AIDS patients was significantly lower than that produced by CD4 clones from controls. Both the proportion of γ-IFN-producing CD4 clones and the mean concentration of γ-IFN produced by CD4 clones were significantly lower in AIDS patients than in controls. In contrast, there were no differences between AIDS patients and normal individuals in the proportion of IL-2- or Y-IFN-producing CD8 clones, or in the mean concentration of IL-2 and v-IFN produced by CD8 clones. These data suggest that the reduced ability of PB T-cells from patients with AIDS to produce IL-2 and v-IFN is not simply due to altered proportions or numbers of T-cell sub-populations, but also reflects intrinsic abnormalities of individual CD4 T lymphocytes.

scholarly journals Self-reactive human CD4 T cell clones form unusual immunological synapses

2012 ◽  
Vol 209 (2) ◽  
pp. 335-352 ◽  
Author(s):  
David A. Schubert ◽  
Susana Gordo ◽  
Joseph J. Sabatino ◽  
Santosh Vardhana ◽  
Etienne Gagnon ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Receptor ◽  
Tcr Signaling ◽  
T Cell Clones ◽  
Cell Clones ◽  
Immunological Synapses ◽  
High Degree ◽  
Self Antigen

Recognition of self–peptide-MHC (pMHC) complexes by CD4 T cells plays an important role in the pathogenesis of many autoimmune diseases. We analyzed formation of immunological synapses (IS) in self-reactive T cell clones from patients with multiple sclerosis and type 1 diabetes. All self-reactive T cells contained a large number of phosphorylated T cell receptor (TCR) microclusters, indicative of active TCR signaling. However, they showed little or no visible pMHC accumulation or transport of TCR–pMHC complexes into a central supramolecular activation cluster (cSMAC). In contrast, influenza-specific T cells accumulated large quantities of pMHC complexes in microclusters and a cSMAC, even when presented with 100-fold lower pMHC densities. The self-reactive T cells also maintained a high degree of motility, again in sharp contrast to virus-specific T cells. 2D affinity measurements of three of these self-reactive T cell clones demonstrated a normal off-rate but a slow on-rate of TCR binding to pMHC. These unusual IS features may facilitate escape from negative selection by self-reactive T cells encountering very small amounts of self-antigen in the thymus. However, these same features may enable acquisition of effector functions by self-reactive T cells encountering large amounts of self-antigen in the target organ of the autoimmune disease.

Ten Year Survival in Patients with Myeloma Is Characterized by the Persistence of Immunological Control Which Is Detected by Immunological Biomarkers

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1818-1818
Author(s):  
Ross D Brown ◽  
Hayley Suen ◽  
Christian E Bryant ◽  
Shihong Yang ◽  
James Favaloro ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Conflicts Of Interest ◽  
Cytotoxic T Cells ◽  
Interferon Γ ◽  
Tumor Control ◽  
T Cell Clones ◽  
Tumour Control ◽  
Cell Clones ◽  
Split Anergy

Abstract Abstract 1818 There is clinical evidence for the presence of a limited degree of host-tumor control in patients with multiple myeloma (MM) but the exact mechanisms involved are not known. Patients who survive for more than ten years are likely to have the most active immunological host-tumour control and are an ideal cohort to study. We now add to our preliminary observations using a range of immunological biomarkers in the 29 of these patients who attend our clinic. 51% of MM patients (n=264) had expanded CD3+CD8+ TCRVβ+ CD57+T cell clones detected by TCRVβ analysis (Beckman, BetaMark). Clonality was confirmed by IgH CDR3 sequencing. These clones accounted for 14.3% (median) of the CD3 cells (range 4–49%). CFSE tracking demonstrated the anergic nature of these clonal T cells (median 6% proliferation) compared with other CD8 cells (70% proliferation) while Geneset analysis of mRNA microarrays (Affymetrix U133) identified that anergy was caused by upregulated RAS, CSK, TOB and suppressed ERK pathways. Unlike recent reports for T-LGL, microarray analysis suggested that there was no evidence of STAT3 upregulation in the MM T cell clones. Functional studies suggested that these non-proliferating clones have split anergy as interferon-γ production was normal. In contrast, all ten year survivors had expanded T cell clones and serial studies demonstrated a >8 year persistence of the same clone in 8 out of 12 patients studied. More importantly, unlike the other MM patients, the T cell clones in 19 out of 21 of the ten year survivors studied were not anergic. The Treg/Th17 ratio in the ten year survivors was significantly lower than other MM patients (median 1.9 vs 12.0; p<0.0002) and even lower than age matched normals (median 5.6; p<0.006). This difference in the ten year survivors was due to an increased absolute Th17 cell (p<0.005) number and a reduced absolute Tregnumber (p<0.05). MM patients had a reduced number of absolute 6-Sulfo-LacNAc (SLAN)-DCs, a major source of IL-12, compared to both age matched controls and long term survivors (p < 0.01). Allo SLAN-DCs stimulated a higher proliferative response by MM T cells than could be achieved with mononuclear preparations. In conclusion, MM patients have expanded clones of cytotoxic T cells that exhibit split anergy and these cells are potential candidates for restoring immunological control of MM and other cancers. The normalised Treg/Th17 ratio suggests that the induced tolerance associated with increased Treg cell numbers is also absent in these patients. Our observations that the ten year MM survivors do not have anergy in their clonal T cells and have less Treg suppression offers a unique cohort for future studies. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Regional and clonal T cell dynamics at single cell resolution in immune checkpoint blockade

2021 ◽  
Author(s):  
Joy A. Pai ◽  
Andrew Chow ◽  
Jennifer Sauter ◽  
Marissa Mattar ◽  
Hira Rizvi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Immune Checkpoint ◽  
Cd8 T Cell ◽  
Immune Checkpoint Blockade ◽  
Rna Seq ◽  
Cell Dynamics ◽  
T Cell Clones ◽  
Cell Clones

Paired T cell receptor and RNA single cell sequencing (scTCR/RNA-seq) has allowed for enhanced resolution of clonal T cell dynamics in cancer. Here, we report a scTCR/RNA-seq dataset of 162,062 single T cells from 31 tissue regions, including tumor, adjacent normal tissues, and lymph nodes (LN), from three patients who underwent resections for progressing lung cancers after immune checkpoint blockade (ICB). We found marked regional heterogeneity in tumor persistence that was associated with heterogeneity in CD4 and CD8 T cell phenotypes; regions with persistent cancer cells were enriched for follicular helper CD4 T cells (TFH), regulatory T cells (Treg), and exhausted CD8 T cells. Clonal analysis demonstrated that highly-expanded T cell clones were predominantly of the CD8 subtype, were ubiquitously present across all sampled regions, found in the peripheral circulation, and expressed gene signatures of 'large' and 'dual-expanded' clones that have been predictive of response to ICB. Longitudinal tracking of CD8 T cell clones in the peripheral blood revealed that the persistence of ubiquitous CD8 T cell clones, as well as phenotypically distinct clones with tumor-reactive features, correlated with systemic tumor control. Finally, tracking CD8 T cell clones across tissues revealed the presence of TCF-1+ precursor exhausted CD8 T cells in tumor draining LNs that were clonally linked to expanded exhausted CD8 T cells in tumors. Altogether, this comprehensive scTCR/RNA-seq dataset with regional, longitudinal, and clonal resolution provides fundamental insights into the tissue distribution, persistence, and differentiation trajectories of ICB-responsive T cells that underlie clinical responses to ICB.

High Avidity PRAME Specific T Cells Derived From In Vivo HLA Mismatched Transplantation Setting Potentially Useful for Immunotherapeutic Strategies.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4087-4087 ◽  
Author(s):  
Avital L. Amir ◽  
Dirk M. van der Steen ◽  
Renate S. Hagedoorn ◽  
Marieke Griffioen ◽  
J.H. Frederik Falkenburg ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Epithelial Cells ◽  
Cell Lines ◽  
High Avidity ◽  
T Cell Clones ◽  
Cell Clones ◽  
T Cell Clone ◽  
Self Antigens

Abstract Abstract 4087 Poster Board III-1022 Adoptive T cell therapy is an attractive strategy to provide cancer patients with antigen specific T cells. For this approach T cells with specificity for non-polymorphic tumor-associated self-antigens that are shared between various tumors are promising candidates. However, the isolation of high avidity T cells specific for nonpolymorphic tumor associated self-antigens is difficult, because of self-tolerance. During thymic selection T cells that exhibit high avidity for self-antigens presented by self-HLA are deleted by positive and negative selection. This explains why most T cells directed against non-polymorphic tumor associated self-antigens characterized to date exhibit low to intermediate avidity. After HLA mismatched stem cell transplantation (SCT) however, T cells educated in the donor have not encountered the allogeneic HLA molecules from the patient during thymic selection. Consequently, these T cells can exhibit high avidity for tumor associated antigens presented by allogeneic patient HLA molecules. In this study we aimed to identify T cells directed against non-polymorphic tumor associated antigens using an in vivo HLA mismatched transplantation setting. Alloreactive T cell clones were isolated and expanded from a patient that experienced graft versus leukemia as well as acute graft versus host disease following HLA-A2 mismatched SCT and donor lymphocyte infusion for the treatment of AML. All isolated T-cell clones were allo-HLA-A2 reactive, and by loading of T2 cells with HPLC fractionations of peptides eluted from HLA-A2 we were able to demonstrate that all alloreactive clones recognized one single fraction, indicative for peptide specific recognition. By two additional peptide HPLC fractionation rounds and mass spectrometry we were able to characterize the peptides of 8 different allo-HLA-A2 reactive T cell clones. One of the T cell clones, was of particular interest since this T cell clone recognized the peptide SLLQHLIGL derived from the preferentially expressed antigen on melanomas (PRAME). Recognition by the clone of HLA-A2 positive COS cells transfected with PRAME, and tetramer staining of the clone, confirmed the specificity against the PRAME derived peptide. Peptide titration demonstrated that the PRAME specific T cell clone exhibited high affinity for the SLL peptide. Since PRAME is overexpressed in a large fraction of tumors, we analyzed whether the PRAME specific clone could recognize HLA-A2 expressing tumor cell lines. The results demonstrated that all 8 tested melanoma cell lines, 2 of 3 RCC cell lines, 1 of 2 mamma carcinoma cell lines and 1 of 2 lung carcinoma cell lines were recognized by the clone. In addition, 5 out of 10 primary acute myeloid leukemia cells, and 2 out of 3 acute lymphoblastic leukemia cell lines were recognized. Since it has been described that also certain normal tissues express low levels of PRAME, the clone was tested against numerous HLA-A2 positive non-malignant cells. No reactivity against fibroblasts, keratinocytes, bronchus epithelial cells, hepatocytes, billiair duct epithelial cells, colon epithelial cells, mesenchymal stem cells, (activated) B-cells, (activated) T cells, monocytes and CD34+ cells was observed. However, the clone demonstrated high reactivity against monocyte derived DC's and a low but significant reactivity against primary tubular epithelial cells. By quantitative PCR we demonstrated that the level of recognition of the different cell types is correlated with the expression levels of PRAME. The results demonstrate that the high avidity PRAME specific T cells clone, derived from an in vivo allo-HLA-A2 immune response, is solely PRAME specific and exerts high reactivity against numerous tumors and limited of target toxicity. Based on these results we conclude that the high affinity TCR from this high avidity PRAME specific T cell may be an effective tool for adoptive T cell therapy using TCR gene modified T cells for the treatment of cancer patients. Disclosures: No relevant conflicts of interest to declare.

High-Affinity CD20-Specific T-Cell Receptors Suitable for Adoptive Immunotherapy in the Treatment of CD20low B-Cell Malignancies

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3837-3837
Author(s):  
Lorenz Jahn ◽  
Pleun Hombrink ◽  
Chopie Hassan ◽  
Michel G.D. Kester ◽  
Renate S. Hagedoorn ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
High Avidity ◽  
B Cell Malignancies ◽  
T Cell Clones ◽  
High Affinity ◽  
Cell Clones ◽  
Cd20 Expression ◽  
Self Antigens

Abstract Therapeutic monoclonal antibodies (mAb) such as Rituximab and Ofatumumab have demonstrated the clinical efficacy of targeting the B-cell restricted antigen CD20 for the treatment of B-cell lymphomas and leukemia. Although CD20 is also expressed on healthy B-cell cells which are depleted in the course of therapy, long-term B-cell aplasia is well manageable. However, non-responsive or refractory disease to CD20-targeted mAb treatment has been reported with various mechanisms of resistance: downregulation of CD20 expression, internalization of CD20:mAb complex, inhibition of complement-dependent cytotoxicity and absence of an effector cell repertoire in patients treated with chemotherapy prior to mAb infusion. Therefore, additional therapeutic strategies are required. T-cell receptor (TCR) gene transfer is an attractive strategy to equip T-cells with TCRs of defined antigen-specificity. Due to their high sensitivity for cognate antigen presented in HLA, TCRs can induce T-cell activation even when antigen expression is very low. However, the broad application of TCR-based adoptive immunotherapy directed against self-antigens such as CD20 is hampered by lack of an effective immune response against self-antigens. T-cells carrying high-affinity TCRs reactive to such self-antigens are deleted by negative selection during thymic development to prevent auto-reactivity. An attractive strategy to target self-antigens is to exploiting the immunogenicity of such antigens presented in the context of allogeneic HLA (alloHLA). Here, we used the CD20-derived peptide SLFLGILSV (CD20SLF) binding in HLA-A2 to isolate CD20-reactive T-cells carrying high-affinity TCRs. From peripheral blood mononuclear cells of HLA-A*0201 (HLA-A2)-negative healthy individuals CD8+ T-cells binding to peptide-HLA tetramers composed of CD20SLF bound to HLA-A2 were isolated and clonally expanded. Two high-avidity T-cell clones were identified specific for HLA-A2-bound CD20SLF. CD20-dependent recognition was demonstrated for both clones by transducing the CD20 gene in HLA-A2-positive cell lines which otherwise lack CD20 expression. Both CD20-specific T-cell clones efficiently recognized CD20-expressing HLA-A2-positive primary B-cell malignancies including acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). In addition, the CD20-specific T-cell clones were able to more efficiently recognize ALL cell-lines than CD20-specific mAbs. We demonstrated that on target cells with only very low CD20 surface expression, the CD20-specific T-cell clones could still efficiently recognize endogenously processed CD20-derived peptide in the context of HLA-A2. Furthermore, no recognition of HLA-A2-positive but CD20-negative cell subsets including CD34+hematopoietic progenitor cells, T-cells, immature and mature dendritic cells could be demonstrated. Additionally, recognition of HLA-A2-positive non-hematopoietic cells such as fibroblasts even under simulated inflamed conditions was absent. Transduction of the identified TCRs resulted in efficient expression of the introduced CD20-specific TCRs and conferred CD20-specificity onto recipient cells. In summary, we exploited the immunogenicity of alloHLA to raise high-avidity T-cells against self-antigens such as CD20. The identified CD20-specific T-cell clones efficiently recognized CD20-expressing primary ALL, CLL and MCL. These T-cells clones more efficiently recognized B-cell malignancies than CD20-targeted mAbs while no recognition of CD20-negative hematopoietic and non-hematopoietic cells was observed. Transduction of these CD20-specific TCRs conferred CD20-specificity onto recipient cells. These CD20-specific TCRs can be useful to treat patients with CD20low B-cell malignancies by administering TCR-engineered T cells with potent effector function. Disclosures No relevant conflicts of interest to declare.

scholarly journals A minority of T cells recognizing tumor-associated antigens presented in self-HLA can provoke antitumor reactivity

Blood ◽  
2020 ◽  
Vol 136 (4) ◽  
pp. 455-467 ◽  
Author(s):  
Marthe C. J. Roex ◽  
Lois Hageman ◽  
Sabrina A. J. Veld ◽  
Esther van Egmond ◽  
Conny Hoogstraten ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Clone ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
T Cell Clones ◽  
Tumor Associated Antigens ◽  
Cell Clones ◽  
T Cell Clone ◽  
Self Antigens

Abstract Tumor-associated antigens (TAAs) are monomorphic self-antigens that are proposed as targets for immunotherapeutic approaches to treat malignancies. We investigated whether T cells with sufficient avidity to recognize naturally overexpressed self-antigens in the context of self-HLA can be found in the T-cell repertoire of healthy donors. Minor histocompatibility antigen (MiHA)-specific T cells were used as a model, as the influence of thymic selection on the T-cell repertoire directed against MiHA can be studied in both self (MiHApos donors) and non-self (MiHAneg donors) backgrounds. T-cell clones directed against the HLA*02:01-restricted MiHA HA-1H were isolated from HA-1Hneg/HLA-A*02:01pos and HA-1Hpos/HLA-A*02:01pos donors. Of the 16 unique HA-1H–specific T-cell clones, five T-cell clones derived from HA-1Hneg/HLA-A*02:01pos donors and one T-cell clone derived from an HA-1Hpos/HLA-A*02:01pos donor showed reactivity against HA-1Hpos target cells. In addition, in total, 663 T-cell clones (containing at least 91 unique clones expressing different T-cell receptors) directed against HLA*02:01-restricted peptides of TAA WT1-RMF, RHAMM-ILS, proteinase-3-VLQ, PRAME-VLD, and NY-eso-1-SLL were isolated from HLA-A*02:01pos donors. Only 3 PRAME-VLD–specific and one NY-eso-1-SLL–specific T-cell clone provoked interferon-γ production and/or cytolysis upon stimulation with HLA-A*02:01pos malignant cell lines (but not primary malignant samples) naturally overexpressing the TAA. These results show that self-HLA–restricted T cells specific for self-antigens such as MiHA in MiHApos donors and TAAs are present in peripheral blood of healthy individuals. However, clinical efficacy would require highly effective in vivo priming by peptide vaccination in the presence of proper adjuvants or in vitro expansion of the low numbers of self-antigen–specific T cells of sufficient avidity to recognize endogenously processed antigen.

scholarly journals Ex Vivo Monitoring of Antigen-Specific CD4+ T Cells after Recall Immunization with Tetanus Toxoid

2007 ◽  
Vol 14 (9) ◽  
pp. 1108-1116 ◽  
Author(s):  
Catherine Barbey ◽  
Estelle Pradervand ◽  
Nathalie Barbier ◽  
François Spertini
Keyword(s):  
Flow Cytometry ◽  
T Cells ◽  
T Cell ◽  
Tetanus Toxoid ◽  
Ex Vivo ◽  
Interleukin 2 ◽  
Effector Memory ◽  
Specific Response ◽  
T Cell Clones ◽  
Cell Clones

ABSTRACT To monitor antigen-specific CD4+ T cells during a recall immune response to tetanus toxoid (TT), a sequential analysis including ex vivo phenotyping and cytokine flow cytometry, followed by cloning and T-cell-receptor (TCR) spectratyping of cytokine-positive CD4+ T cells, was performed. Grossly, twice as many TT-specific CD4+ T-cell clones, ex vivo derived from the CCR7+/− CD69+ interleukin-2-positive (IL-2+) CD4+ subsets, belonged to the central memory (TCM; CD62L+ CD27+ CCR7+) compared to the effector memory population (TEM; CD62L− CD27− CCR7−). After the boost, a predominant expansion of the TCM population was observed with more limited variations of the TEM population. TCR beta-chain-variable region (BV) spectratyping and sequencing confirmed a large concordance between most frequently expressed BV TCR-CDR3 from ex vivo-sorted CCR7+/− CD69+ IL-2+ CD4+ subsets and BV usage of in vitro-derived TT-specific CD4+ T-cell clones, further demonstrating the highly polyclonal but stable character of the specific recall response to TT. Taken together, ex vivo flow cytometry analysis focused on the CCR7+/− CD69+ IL-2+ CD4+ subsets appears to target the bulk of antigen-specific T cells and to reach an analytical power sufficient to adequately delineate in field trials the profile of the antigen-specific response to vaccine.

scholarly journals A novel subset of CD2-, CD3/T cell receptor alpha/beta+ human peripheral blood T cells. Phenotypic and functional characterization of interleukin 2-dependent CD2-CD3+ T cell clones.

1989 ◽  
Vol 170 (2) ◽  
pp. 559-569 ◽  
Author(s):  
D Kabelitz ◽  
P Conradt ◽  
S Schondelmaier ◽  
H Wagner ◽  
R Haars
Keyword(s):  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Sheep Erythrocyte ◽  
Interleukin 2 ◽  
Normal Peripheral Blood ◽  
T Cell Clones ◽  
Cell Clones ◽  
Alpha Beta ◽  
A Minor

It is generally believed that CD2 (T11, sheep erythrocyte receptor) is expressed on all human T cells. In the present study we have identified and characterized a minor subset of CD2- CD3/TCR alpha/beta+ T cells in the peripheral blood of healthy individuals. CD2-CD3+ T cells were enriched in PBMC depleted of plastic-adherent macrophages, E-rosetting (i.e., CD2+) T cells and surface Ig+ B cells. CD2-CD3+ T cells accounted for 0.1-0.8% of PBMC in six individuals. IL-2-dependent long-term clones of CD2-CD3+ T cells neither reacted with a panel of anti-CD2 mAbs nor expressed detectable levels of CD2 mRNA by Northern blot analysis. These clones, however, expressed a full-length TCR C beta mRNA and reacted with mAbs against TCR-alpha/beta, CD3, and CD4, and thus were mature T cells. CD2-CD3/TCR+ T cell clones could be triggered into proliferation, IL-2 production, and cytotoxic effector activity by anti-CD3 and anti-TCR mAbs. We conclude that (a) a minor subset of CD2-, CD3/TCR-alpha/beta+ T cells is present in normal peripheral blood; and (b) expression of CD2 at the level of protein and/or mRNA is not required for T cell signaling via the CD3/TCR molecular complex.

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