Tracking down cryptic peptides

June 23, 2020

Almost all cells of the human body present fragments of cellular proteins on their surface, so-called human leukocyte antigens or HLA peptides, which play an important role in the immune response. If the immune system detects foreign HLA peptides, such as viral peptides on a virus-infected cell or mutated peptides on a tumour cell, T-cells eliminate the corresponding cell. The entirety of the HLA peptides presented on a cell is referred to as the cell´s immunopeptidome.

New approach enables comprehensive analysis for the first time

Besides the usual HLA peptides, there are also cryptic HLA peptides. These are derived from specific RNA sequences that do not contain information for a specific protein as is usually the case. Over the last few decades, only a few cryptic HLA peptides have been identified because they are very small and are quickly degraded in the cells. On the other hand, efficient computer algorithms for the analysis were lacking.

In a completely new approach, the Würzburg scientists have now combined several analytical methods that are particularly suitable for small peptides. "Using a novel bioinformatics method developed by us, for the first time we were able to identify thousands of cryptic HLA peptides in the immunopeptidomes of a wide variety of tumors such as melanoma and breast cancer," explains Dr. Andreas Schlosser, research group leader at the Rudolf Virchow Center at Julius-Maximilians-Universität (JMU) Würzburg in Bavaria, Germany.

The new bioinformatics approach is based exclusively on data from mass spectrometry, a method for determining the mass of molecules such as Peptides. This makes it possible to systematically and comprehensively determine the cryptic HLA peptides. In addition, it was possible to clarify on which cells and to what extent cryptic peptides are present: "We were able to show that cryptic HLA peptides make up a significant part of the immunopeptidomes of tumors," explains Prof. Dr. Florian Erhard, group leader at the JMU Institute of Virology.

Effective points of attack for the immune system

It was already known from individual studies that cryptic peptides can trigger autoimmune reactions such as in diabetes type 1 as well as immune responses against tumor cells. The new analyses provide evidence that certain cryptic HLA peptides are exclusively found on tumour cells. Such tumour-specific cryptic HLA peptides might thus prove to be worthwhile target structures for cancer immunotherapies. Scientists at the University of Würzburg and the University Hospital of Würzburg are already examining a selection of the identified peptides to determine whether they are suitable as targets for cancer immunotherapy.

Virus-infected cells also present cryptic HLA peptides that could be used as a target structure for vaccines. With their new method, the researchers thus have an effective tool in hand to learn more about the general function and formation of cryptic peptides. "We hope that our bioinformatics approach will provide us with a better understanding of autoimmune reactions as well as immune reactions against tumour cells and virus-infected cells," says Schlosser.
-end-


University of Würzburg

Related Tumor Cells Articles from Brightsurf:

A more sensitive way to detect circulating tumor cells
Breast cancer is the most frequently diagnosed cancer in women, and metastasis from the breast to other areas of the body is the leading cause of death in these patients.

Cancer researchers train white blood cells to attacks tumor cells
Scientists at the National Center for Tumor Diseases Dresden (NCT/UCC) and Dresden University Medicine, together with an international team of researchers, were able to demonstrate that certain white blood cells, so-called neutrophil granulocytes, can potentially - after completing a special training program -- be utilized for the treatment of tumors.

How to prevent the spread of tumor cells via the lymph vessels
Scientists from the German Cancer Research Center and the Mannheim Medical Faculty of the University of Heidelberg identified a new way to block the dangerous spread of tumor cells via lymphatic vessels.

The CNIO reprograms CRISPR system in mice to eliminate tumor cells without affecting healthy cells
CNIO researchers destroyed Ewing's sarcoma and chronic myeloid leukaemia tumor cells by using CRISPR to cut out the fusion genes that cause them.

Feeding off fusion or the immortalization of tumor cells
Despite all recent progress, cancer remains one of the deadliest human diseases.

How do tumor cells divide in the crowd?
Scientists led by Dr. Elisabeth Fischer-Friedrich, group leader at the Excellence Cluster Physics of Life (PoL) and the Biotechnology Center TU Dresden (BIOTEC) studied how cancer cells are able to divide in a crowded tumor tissue and connected it to the hallmark of cancer progression and metastasis, the epithelial-mesenchymal transition (EMT).

How tumor cells evade the immune defense
Scientists are increasingly trying to use the body's own immune system to fight cancer.

Engineered immune cells recognize, attack human and mouse solid-tumor cancer cells
CAR-T therapy has been used successfully in patients with blood cancers such as lymphoma and leukemia.

New pathway to attack tumor cells identified
A study led by the Institut de Neurociències (INc-UAB) describes a new strategy to tackle cancer, based on inducing a potent stress in tumor causing cell destruction by autophagy.

Nutrient deficiency in tumor cells attracts cells that suppress the immune system
A study led by IDIBELL researchers and published this week in the American journal PNAS shows that, by depriving tumor cells of glucose, they release a large number of signaling molecules.

Read More: Tumor Cells News and Tumor Cells Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.