Breaking News
November 13, 2018 - FDA Approves Keytruda (pembrolizumab) in Combination with Carboplatin and Either Paclitaxel or Nab-Paclitaxel for the First-Line Treatment of Patients with Metastatic Squamous Non-Small Cell Lung Cancer (NSCLC)
November 13, 2018 - Scientists take big step toward finding non-addictive painkiller
November 13, 2018 - Diabetes medication reduces risk of heart failure hospitalization
November 13, 2018 - Achieving high follow-up rates for violently injured patient population is feasible
November 13, 2018 - Shortage of specific gene ‘silencing’ molecules linked with pediatric low-grade gliomas
November 13, 2018 - Abx-Resistant Enterobacteriaceae Tied to Clinical Failure in UTI
November 13, 2018 - US approves first new type of flu drug in 2 decades
November 13, 2018 - Is zinc the link to how we think? Some evidence, and a word of warning
November 13, 2018 - Dispelling taboos, Michelle Obama talks IVF and miscarriage
November 13, 2018 - Medical experts discuss future challenges of healthcare at HSMA’s inaugural conference
November 13, 2018 - Growth and spread of deadly eye tumor suppressed in cells, animals
November 12, 2018 - Study finds huge shortfall in use of home-based medical care by frail seniors
November 12, 2018 - Cocaine Cut With Anti-Worming Drug, Levamisole, May Cause Brain Damage
November 12, 2018 - Obese mice lose a third of their fat using a natural protein
November 12, 2018 - Behind many a Parkinson’s case lurks a mutation in a gene called LRRK2 — why?
November 12, 2018 - Drug with fish oil cuts risk of heart attack, stroke, study finds
November 12, 2018 - Mild exposure to single blast can induce meaningful pathogenic effects, study shows
November 12, 2018 - Miniature pacemakers aim to make heart procedures for infants less invasive, more efficient
November 12, 2018 - Treating pre-cancerous stem cells at early stage could be key to preventing bowel cancer
November 12, 2018 - Kawasaki disease triggered by a combination of factors
November 12, 2018 - Optibrium and University of Nottingham Collaborate on Innovative Teaching Programme
November 12, 2018 - RNA defects linked to multiple myeloma progression in high risk patients
November 12, 2018 - Science is on trial – and we need doctors to provide the defense
November 12, 2018 - Salk researchers receive $19.2 million to unravel mysteries of age-related cognitive decline
November 12, 2018 - KE Eye Centers offer new solution for patients with myopia and astigmatism
November 12, 2018 - Trumpeted new Medicare Advantage benefits will be hard for seniors to find
November 12, 2018 - Biogen and Eisai Announce Presentation of Detailed Analyses from the Phase 1b Long-Term Extension Study of Aducanumab at Clinical Trials on Alzheimer’s Disease (CTAD)
November 12, 2018 - Scientists reveal new cystic fibrosis treatments work best in inflamed airways
November 12, 2018 - Hands-Only CPR training kiosks can teach life-saving skills in just minutes
November 12, 2018 - Inexpensive and effective drug does not reduce major adverse cardiovascular event rates
November 12, 2018 - Testing coronary calcium levels can better predict patient’s risk for coronary heart disease
November 12, 2018 - FDA conducts mass seizure of food and medical products held under insanitary conditions
November 12, 2018 - FDA Approves Invokana (canagliflozin) to Reduce the Risk of Heart Attack, Stroke or Cardiovascular Death in Adults with Type 2 Diabetes and Established Cardiovascular Disease
November 12, 2018 - Hormone helps reverse brain damage caused by obesity
November 12, 2018 - Grants aim to provide better cancer clinical trial access for military veterans
November 12, 2018 - Mitochondrial DNA may have strong influence on cellular metabolism and disease susceptibility
November 12, 2018 - High stakes, entrenched interests and the Trump rollback of environmental regs
November 12, 2018 - Stem cells transplanted for treatment of Parkinson’s disease
November 12, 2018 - Sandoz Inc. Issues Voluntary Nationwide Recall of One Lot of Losartan Potassium and Hydrochlorothiazide Due to the Detection of Trace Amounts of NDEA (N-Nitrosodiethylamine) Impurity Found in the Active Pharmaceutical Ingredient (API)
November 12, 2018 - Protein found in patients with severe asthma can help identify who would benefit from targeted drugs
November 12, 2018 - Experts develop a list of competencies in antimicrobial prescribing and stewardship
November 12, 2018 - Allied BioScience receives approved label from EPA for new bacteriostatic surface coating
November 12, 2018 - MR Solutions displays elegant bench top CT scanner with clip-on PET and SPECT at EANM congress
November 12, 2018 - FDA announces emergency use authorization of Ebola fingerstick test with portable reader
November 12, 2018 - Grieving spouses with sleep problems have increased risk of chronic immune activation
November 12, 2018 - Exercise routines affect mental health in Japanese expatriates
November 12, 2018 - Fish oil and vitamin D pills no guard against cancer or serious heart trouble
November 12, 2018 - Excess Gestational Weight Gain Not Better for Child Bone Health
November 12, 2018 - Immune receptor provides protective immunity against Group A Streptococcus
November 12, 2018 - Scientists develop new method to produce irradiated nanomaterials for medical applications
November 12, 2018 - Blue light exposure decreases blood pressure
November 12, 2018 - Researchers discover two proteins essential for development of skeletal muscle
November 12, 2018 - Yelp reviews help understand strengths, weaknesses of emergency departments and urgent care centers
November 12, 2018 - Adolescent obesity linked with increased risk of pancreatic cancer later in life
November 12, 2018 - AHA: Poor Teeth-Brushing Habits Tied to Higher Heart Risk
November 12, 2018 - Researchers find how natural killer cells regulate protective HIV antibodies
November 12, 2018 - Rutgers receives $4.2 million federal grant to improve mental health services
November 12, 2018 - Sussex scientists develop a piece of hardware to show how brains function
November 12, 2018 - Study shows pivotal role of parents in efforts to change sexual orientation of LGBT teens
November 12, 2018 - Neck scan detects dementia way before symptoms appear
November 12, 2018 - Risk-profiling can benefit HIV prevention
November 12, 2018 - New thrombolytic based on magnetite nanoparticles successfully tested on animals
November 12, 2018 - Smoking rates go down in the US, lowest since 1965
November 12, 2018 - Phase III Trial of Darolutamide in Patients with Non-metastatic Castration-resistant Prostate Cancer Meets Primary Endpoint
November 12, 2018 - Moderate exercise before conception resulted in lower body weight, increased insulin sensitivity of offspring
November 11, 2018 - Community choirs for older adults reduce loneliness and increase interest in life
November 11, 2018 - Trevena Receives Complete Response Letter for Oliceridine from FDA
November 11, 2018 - More adults and children are using yoga and meditation
November 11, 2018 - Female smokers at greater risk of heart attacks, finds study
November 11, 2018 - Happy Childhood Memories Associated With Better Health
November 11, 2018 - X-linked infantile spinal muscular atrophy – Genetics Home Reference
November 11, 2018 - RNA thought to spread cancer shows ability to suppress breast cancer metastasis
November 11, 2018 - Study finds that thymus plays key role during normal pregnancy
November 11, 2018 - Exploring why some athletes ice their muscles after exercise
November 11, 2018 - Female Genital Mutilation Decreasing in African Nations
November 11, 2018 - Are humans immune to the CRISPR-Cas9 gene editing scissors?
November 11, 2018 - Breastmilk and saliva mixtures regulate oral microbiome of newborn babies
November 11, 2018 - Learning familiar faces through social interactions reduces variability in face recognition
November 11, 2018 - New open source decision support tool could help clinicians chose chemotherapy drugs
November 11, 2018 - New weapons drawn in global TB fight
Blood donors’ leftover immune cells reveal secrets of antibody affinity

Blood donors’ leftover immune cells reveal secrets of antibody affinity

image_pdfDownload PDFimage_print

During some kinds of blood donations, you get most of your blood back. For example, platelet donation involves a procedure in which donor blood is filtered to harvest the platelets for medical use and the rest of the blood components are returned to the donor’s body. The byproducts of this procedure – a fraction of immune cells – are typically discarded.

Researchers at Iowa State University, partnering with the LifeServe Blood Center, have used these leftover blood donor cells to gain crucial insights into how natural killer cells circulating in the human body differ from those typically studied in the lab. The results of this research are published in the March 9 issue of the Journal of Biological Chemistry.

Adam Barb, an associate professor of biochemistry at Iowa State, studies the receptor CD16a, which is found on the surface of natural killer cells and binds to the antibody immunoglobulin G (IgG). IgG is the most common antibody produced by the human body to coat the surfaces of pathogens or tumors and signal their destruction by natural killer cells. IgG is used as the basis of most antibody immunotherapies, for example against cancer.

How effectively natural killer cells can destroy their targets depends on how tightly the receptor binds to the antibody. Barb’s team had previously found that the extent of this attraction, or affinity, depended on the types and amounts of carbohydrates attached to the antibody. In the new study, they set out to find how carbohydrate modifications of the receptor in humans affected the antibody-receptor binding affinity.

“We know that (receptors) can be expressed by the natural killer cell in thousands to millions of different forms,” Barb said. “This is because the molecule is coated with complex carbohydrates, like a sugar coat, that can be highly variable.”

Because NK cells are found at a low concentration in human blood, researchers who study these receptors typically insert the gene encoding the receptor into cells that can be grown in culture in the lab, an approach called recombinant expression. But it was not clear whether the conditions in cell culture would result in the same carbohydrate modifications to the receptor that occur in the human body.

“All of the work that had been done at that time…was studied with recombinant material, not from primary sources,” Barb said. “People had assumed, with respect to this receptor, that the mammalian (cells) used for the recombinant expression would provide the correct types of carbohydrates.”

In order to harvest the receptors from the source, Barb’s team turned to a nearby blood bank that performed platelet apheresis, because they knew that a fraction of white blood cells were discarded as part of the filtering procedure.

“When the donor is disconnected from the machine, they don’t get those (lymphocytes) back, and that filter is usually just thrown away,” Barb said. “So basically (they’re) concentrating lymphocytes, including natural killer cells, which is exactly what we want, in these filters.”

Barb’s team obtained these filters from the blood bank and isolated the natural killer cells. They then examined the carbohydrate modifications of receptors from donors’ natural killer cells and how these modifications affected binding to antibodies. They found that the carbohydrate modifications in the patients’ receptors were much less elaborate than those from recombinant receptors, resulting in higher affinity.

“There was much less (carbohydrate) processing that the NK cells did in comparison to any of the forms that were expressed in these recombinant systems,” Barb said. “And as a result of that, the affinity for antibody appears to be higher in natural killer cells than it would be in a receptor that was expressed from recombinant systems. Smaller carbohydrates appear to make for tighter binding interactions.”The study was carried out on natural killer cell samples from donors that were of similar age, sex and blood type, raising the question of how the receptor’s carbohydrate modifications may vary in natural populations.

“There appeared to be some degree of variability between donors,” Barb said “(But) how does that change throughout the lifetime, how does that change in response to infection? All of those questions are absolutely things that we would very much like to investigate very specifically.”

The results suggest that finding ways to influence the carbohydrate modifications of these receptors could be a way to fine-tune antibody-receptor interactions in the context of antibody therapies.


Explore further:
Researchers discover the unexpected role of platelets in immune response

More information:
Kashyap R. Patel et al, Restricted processing of CD16a/Fc γ receptor IIIaN-glycans from primary human NK cells impacts structure and function, Journal of Biological Chemistry (2018). DOI: 10.1074/jbc.RA117.001207

Journal reference:
Journal of Biological Chemistry

Provided by:
American Society for Biochemistry and Molecular Biology

Tagged with:

About author

Related Articles