scholarly journals A conserved energetic footprint underpins recognition of human leukocyte antigen-E by two distinct αβ T cell receptors

2017 ◽  
Vol 292 (51) ◽  
pp. 21149-21158 ◽  
Author(s):  
Lucy C. Sullivan ◽  
Nicholas G. Walpole ◽  
Carine Farenc ◽  
Gabriella Pietra ◽  
Matthew J. W. Sum ◽  
...  
Keyword(s):  
T Cell ◽  
Human Leukocyte Antigen ◽  
T Cell Receptors ◽  
Human Leukocyte ◽  
Cell Receptors ◽  
Leukocyte Antigen

scholarly journals Facile method for screening clinical T cell receptors for off-target peptide-HLA reactivity

2018 ◽  
Author(s):  
Marvin H. Gee ◽  
Xinbo Yang ◽  
K. Christopher Garcia
Keyword(s):  
T Cell ◽  
T Cell Receptors ◽  
Human Leukocyte ◽  
Cross Reactivity ◽  
Affinity Maturation ◽  
Yeast Display ◽  
Cell Therapies ◽  
Cell Receptors ◽  
Leukocyte Antigen ◽  
Clinical Toxicity

ABSTRACTT cell receptors (TCRs) exhibit varying degrees of cross-reactivity for peptides presented by the human leukocyte antigen (HLA). In engineered T cell therapies, TCR affinity maturation is a strategy to improve the sensitivity and potency to often a low-density peptide-HLA (pHLA) target. However, the process of affinity maturation towards a known pHLA complex can introduce new and untoward cross-reactivities that are difficult to detect and raises significant safety concerns. We developed a yeast-display platform of pHLA consisting of ~100 million different 9mer peptides presented by HLA-A*01 and used a previously established selection approach to validate the specificity and cross-reactivity of the A3A TCR, an affinity-matured TCR against the MAGE-A3 target (EVDPIGHLY). We were able to identify reactivity against the titin peptide (ESDPIVAQY), to which there is now known clinical toxicity. We propose the use of yeast-display of pHLA libraries to determine cross-reactive profiles of candidate clinical TCRs to ensure safety and pHLA specificity of natural and affinity-matured TCRs.

scholarly journals Can Glycosylation Mask the Detection of MHC Expressing p53 Peptides by T Cell Receptors?

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1056
Author(s):  
Thanh Binh Nguyen ◽  
David P. Lane ◽  
Chandra S. Verma
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptors ◽  
Human Leukocyte ◽  
Cell Receptors ◽  
Leukocyte Antigen ◽  
Endogenous Peptides ◽  
Histocompatibility Complex ◽  
Normal Individuals

Proteins of the major histocompatibility complex (MHC) class I, or human leukocyte antigen (HLA) in humans interact with endogenous peptides and present them to T cell receptors (TCR), which in turn tune the immune system to recognize and discriminate between self and foreign (non-self) peptides. Of especial importance are peptides derived from tumor-associated antigens. T cells recognizing these peptides are found in cancer patients, but not in cancer-free individuals. What stimulates this recognition, which is vital for the success of checkpoint based therapy? A peptide derived from the protein p53 (residues 161–169 or p161) was reported to show this behavior. T cells recognizing this unmodified peptide could be further stimulated in vitro to create effective cancer killing CTLs (cytotoxic T lymphocytes). We hypothesize that the underlying difference may arise from post-translational glycosylation of p161 in normal individuals, likely masking it against recognition by TCR. Defects in glycosylation in cancer cells may allow the presentation of the native peptide. We investigate the structural consequences of such peptide glycosylation by investigating the associated structural dynamics.

scholarly journals Biased T Cell Receptor Usage Directed against Human Leukocyte Antigen DQ8-Restricted Gliadin Peptides Is Associated with Celiac Disease

Immunity ◽  
2012 ◽  
Vol 37 (4) ◽  
pp. 611-621 ◽  
Author(s):  
Sophie E. Broughton ◽  
Jan Petersen ◽  
Alex Theodossis ◽  
Stephen W. Scally ◽  
Khai Lee Loh ◽  
...  
Keyword(s):  
Celiac Disease ◽  
T Cell ◽  
Human Leukocyte Antigen ◽  
T Cell Receptor ◽  
Human Leukocyte ◽  
Cell Receptor ◽  
Leukocyte Antigen ◽  
Receptor Usage ◽  
Gliadin Peptides

scholarly journals Graft failure after T-cell-depleted human leukocyte antigen identical marrow transplants for leukemia: I. Analysis of risk factors and results of secondary transplants

Blood ◽  
1989 ◽  
Vol 74 (6) ◽  
pp. 2227-2236 ◽  
Author(s):  
NA Kernan ◽  
C Bordignon ◽  
G Heller ◽  
I Cunningham ◽  
H Castro-Malaspina ◽  
...  
Keyword(s):  
Risk Factors ◽  
T Cells ◽  
T Cell ◽  
Human Leukocyte Antigen ◽  
Graft Failure ◽  
Human Leukocyte ◽  
Marrow Transplant ◽  
High Dose ◽  
Leukocyte Antigen ◽  
Major Factors

Abstract Risk factors for graft failure were analyzed in 122 recipients of an allogeneic T-cell-depleted human leukocyte antigen (HLA)-identical sibling marrow transplant as treatment for leukemia. In each case pretransplant immunosuppression included 1,375 to 1,500 cGy hyperfractionated total body irradiation and cyclophosphamide (60 mg/kg/d x 2). No patient received immunosuppression prosttransplant for graft-versus-host disease (GVHD) prophylaxis. Nineteen patients in this group experienced graft failure. The major factors associated with graft failure were transplants from male donors and the age of the patient (or donor). Among male recipients of male donor-derived grafts a low dose per kilogram of nucleated cells, progenitor cells (colony forming unit-GM) and T cells was also associated with graft failure. Additional irradiation to 1,500 cGy, high dose corticosteroids posttransplant, and additional peripheral blood donor T cells did not decrease the incidence of graft failure. In addition, type of leukemia, time from diagnosis to transplant, an intact spleen, or the presence of antidonor leukocyte antibodies did not correlate with graft failure. To ensure engraftment of secondary transplants, further immunosuppression was necessary but was poorly tolerated. However, engraftment and survival could be achieved with an immunosuppressive regimen in which antithymocyte globulin and high dose methylprednisolone were administered both before and after infusions of secondary partially T- cell-depleted marrow grafts.

scholarly journals Differences in Expression of Human Leukocyte Antigen Class II Subtypes and T Cell Subsets in Behçet’s Disease with Arthritis

2019 ◽  
Vol 20 (20) ◽  
pp. 5044 ◽  
Author(s):  
S. M. Shamsul Islam ◽  
Hyoun-Ah Kim ◽  
Bunsoon Choi ◽  
Ju-Yang Jung ◽  
Sung-Min Lee ◽  
...  
Keyword(s):  
T Cell ◽  
Human Leukocyte Antigen ◽  
Behcet’S Disease ◽  
Behçet's Disease ◽  
Human Leukocyte ◽  
Class Ii ◽  
T Cell Subsets ◽  
Healthy Controls ◽  
Leukocyte Antigen ◽  
Active Patients

It has been reported Human Leukocyte Antigen (HLA) gene polymorphism is a risk factor for the development of Behçet’s disease (BD). In this study, the association of HLA class II subtypes HLA-DP, DQ, DR, and T cell subsets in BD patients with arthritis was evaluated. Frequencies of HLA-DP, DQ, DR positive cells, and T cell subsets in peripheral blood leukocytes (PBL) were measured by flow cytometric analysis in BD, and compared to rheumatoid arthritis as disease controls and healthy controls. Frequencies of HLA-DQ were significantly decreased in whole PBL and granulocytes of BD active patients as compared to healthy controls. In monocytes populations, proportions of HLA-DR positive cells were significantly increased in BD active patients as compared to healthy controls. Proportions of CD4+CCR7+ and CD8+CCR7+ cells were significantly higher in BD active patients than in BD inactive in whole PBL. Frequencies of CD4+CD62L- and CD8+CD62L- cells in lymphocytes were significantly decreased in active BD than those in inactive BD. There were also correlations between disease activity markers and T cell subsets. Our results revealed HLA-DP, DQ, and DR expressing cell frequencies and several T cell subsets were significantly correlated with BD arthritis symptoms.

scholarly journals Human Leukocyte Antigen Concordance and the Transmission Risk via Breast‐Feeding of Human T Cell Lymphotropic Virus Type I

2006 ◽  
Vol 193 (2) ◽  
pp. 277-282 ◽  
Author(s):  
Robert J. Biggar ◽  
Jennifer Ng ◽  
Norma Kim ◽  
Michie Hisada ◽  
Hong‐Chuan Li ◽  
...  
Keyword(s):  
T Cell ◽  
Human Leukocyte Antigen ◽  
Breast Feeding ◽  
Virus Type ◽  
Human Leukocyte ◽  
Transmission Risk ◽  
Type I ◽  
Leukocyte Antigen ◽  
Human T Cell
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