Antigen Presentation of a Modified Tumor-Derived Peptide by Tumor Infiltrating Lymphocytes

Dionne, Sara O.; Smith, Margaret H.; Marincola, Francesco M.; Lake, Douglas F.

doi:10.1006/cimm.2001.1893

Cited by 6 publications

(3 citation statements)

References 24 publications

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“…Several reports have shown that, after trogocytosis of MHC class I, trogocytosis-positive T cells (both CD4 + and CD8 + ) may induce cytokine production from responders [101]. TEM images demonstrate that an immune synapse forms between trogocytosis-positive cytotoxic T lymphocytes (CTL) and responding CTL [72] and supports the findings that the trogocytosis-positive cells can be killed by CTL (fratricide) [82,84,[101][102][103].…”

Section: Trogocytosis-positive Cells As Antigen Presenting Cellssupporting

confidence: 66%

“…For example, Helft et al showed in vivo that, when the responding T cell was naïve, trogocytosis-mediated T-T antigen presentation lead to activation and proliferation of the responding cell, while previously activated responders underwent apoptosis [100]. Several reports have shown that, after trogocytosis of MHC class I, trogocytosis-positive T cells (both CD4 + and CD8 + ) may induce cytokine production from responders [101]. TEM images demonstrate that an immune synapse forms between trogocytosis-positive cytotoxic T lymphocytes (CTL) and responding CTL [72] and supports the findings that the trogocytosis-positive cells can be killed by CTL (fratricide) [82,84,[101][102][103].…”

Section: Trogocytosis-positive Cells As Antigen Presenting Cellsmentioning

confidence: 99%

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Lymphocytes and Trogocytosis-Mediated Signaling

Reed

Reichelt

Wetzel

2021

Cells

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Trogocytosis is the intercellular transfer of membrane and membrane-associated molecules. This underappreciated process has been described in a variety of biological settings including neuronal remodeling, fertilization, viral and bacterial spread, and cancer, but has been most widely studied in cells of the immune system. Trogocytosis is performed by multiple immune cell types, including basophils, macrophages, dendritic cells, neutrophils, natural killer cells, B cells, γδ T cells, and CD4+ and CD8+ αβ T cells. Although not expressed endogenously, the presence of trogocytosed molecules on cells has the potential to significantly impact an immune response and the biology of the individual trogocytosis-positive cell. Many studies have focused on the ability of the trogocytosis-positive cells to interact with other immune cells and modulate the function of responders. Less understood and arguably equally important is the impact of these molecules on the individual trogocytosis-positive cell. Molecules that have been reported to be trogocytosed by cells include cognate ligands for receptors on the individual cell, such as activating NK cell ligands and MHC:peptide. These trogocytosed molecules have been shown to interact with receptors on the trogocytosis-positive cell and mediate intracellular signaling. In this review, we discuss the impact of this trogocytosis-mediated signaling on the biology of the individual trogocytosis-positive cell by focusing on natural killer cells and CD4+ T lymphocytes.

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Section: Trogocytosis-positive Cells As Antigen Presenting Cellssupporting

confidence: 66%

Section: Trogocytosis-positive Cells As Antigen Presenting Cellsmentioning

confidence: 99%

Lymphocytes and Trogocytosis-Mediated Signaling

Reed

Reichelt

Wetzel

2021

Cells

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“…In addition to their proliferative response, 10BK.1 cells exert cytotoxic activity against syn‐ and allogeneic target cells after reciprocal antigen peptide presentation 6 . The phenomenon of reciprocal antigen presentation by CTL is not restricted to 10BK.1 cells: murine and human CTL with specificity for viral and tumour derived antigens, respectively, were also shown to proliferate, secrete cytokines, and exert MHC unrestricted bystander lysis after activation by reciprocal peptide presentation 7 , 8 , 9 …”

Section: Introductionmentioning

confidence: 99%

Cytotoxic T cells with reciprocal antigenic peptide presentation function are not generally resistant to mutual lysis

2003

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Summary Cytotoxic T cells normally express major histocompatibility complex class I molecules, to which their T cell antigen receptors are restricted. Therefore, a single cytotoxic T cell can not only act as a cytolytic effector cell, but also as an antigen-presenting cell for other cytotoxic T cells of the same or a different clone. In the present paper, we used a murine cytotoxic T cell clone, 10BK.1, recognizing the ovalbumin-derived peptide OVA257-264 in combination with H-2K b to investigate the consequences of reciprocal antigen presentation by these cytotoxic T cells. These cells proliferate after incubation with the relevant peptide in the absence of added accessory cells, indicating reciprocal antigenic peptide presentation by the cytotoxic T cell. We found that reciprocal lysis of these cells was dependent on the time point of incubation with antigen. We did not observe reciprocal lysis of cytotoxic T cells used 30 days after the last restimulation with antigen. In contrast, 10BK.1 cells used two days after the last restimulation showed an increased capacity for reciprocal lysis. The lytic capacity decreased with time after restimulation. Reciprocal lysis of 10BK.1 cells depended on reciprocal peptide presentation by at least two 10BK.1 cells. Recognition of the antigenic peptide, together with class I molecules on the surface of classical syngeneic target cells did not induce lysis of freshly stimulated 10BK.1 cells, suggesting that reciprocal lysis was not just a consequence of re-activation of the cytotoxic T cells. Reciprocal destruction of freshly activated 10BK.1 cells proceeded independent of CD95/CD95 ligand. Despite an increased secretion of tumour necrosis factor-α by 10BK.1 cells on day 2 after antigen stimulation, compared with cells on day 30 after stimulation, tumour necrosis factor-α was not responsible for the reciprocal destruction of freshly stimulated 10BK.1 cells. Lysis of preactivated 10BK.1 cells was independent of autocrine interleukin-2 production by the cytotoxic T cells, but interleukin-2 was required for optimal priming of cytotoxic T cells for reciprocal lysis.

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Identification of HLA-Cw6.02 and HLA-Cw7.01 allele-specific binding motifs by screening synthetic peptide libraries

et al. 2004

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Unlike HLA-A and HLA-B, few peptide epitope motifs have been reported for HLA-C molecules. However, a number of cytotoxic T-lymphocyte epitopes derived from tumor antigens that bind to HLA-C molecules have been described. Here we report peptide-binding motifs for both HLA-Cw6.02 and HLA-Cw7.01 molecules. Recombinant human HLA molecules were generated and used to screen combinatorial 9mer peptide libraries. Complexes of HLA molecules properly folded and associated with beta2-microglobulin and peptides were identified using a conformation-specific HLA class I antibody conjugated to alkaline phosphatase. In the presence of substrate, peptide beads can be readily isolated and microsequenced to determine peptide identity. Of the peptides that bound to HLA-Cw6.02 and HLA-Cw7.01, 19 and 18 peptides, respectively, were sequenced, allowing motif identification for each C allele. This is the first report of an HLA-Cw7.01 peptide motif and extends the findings of Falk et al. [(1993) Proc Natl Acad Sci USA 90:12005] for an HLA-Cw6.02 motif. Anchoring amino acids for the HLA-Cw6.02 motif were phenylalanine or tyrosine in position (P)1, arginine in P2, and an aliphatic/aromatic residue at P9. Anchoring residues for HLA-Cw7.01 were positively charged amino acids in P1 and P2. Unlike most other HLA molecules, we were unable to assign P9 an anchoring residue, and we suspect that HLA-Cw7.01 binds peptides in an unconventional manner. Additionally, preferred amino acids were identified for both molecules. Identification of HLA-Cw6.02 and HLA-Cw7.01 peptide-binding motifs makes a significant contribution to the C allele peptide-binding motifs and will allow investigators to predict, design, and test HLA-Cw6.02 and HLA-Cw7.01 engineered peptides for immunotherapy.

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Antigen Presentation of a Modified Tumor-Derived Peptide by Tumor Infiltrating Lymphocytes

Cited by 6 publications

References 24 publications

Lymphocytes and Trogocytosis-Mediated Signaling

Lymphocytes and Trogocytosis-Mediated Signaling

Cytotoxic T cells with reciprocal antigenic peptide presentation function are not generally resistant to mutual lysis

Identification of HLA-Cw6.02 and HLA-Cw7.01 allele-specific binding motifs by screening synthetic peptide libraries

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