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Related Concept Videos

Cells of the Adaptive Immune Response01:23

Cells of the Adaptive Immune Response

The T and B lymphocytes of the adaptive immune system develop from common lymphoid progenitor cells in the bone marrow. These progenitors give rise to precursors that eventually develop into both T and B lymphocytes. As these precursors mature, they gain the ability to detect and respond to foreign antigens in the body, a process known as immunocompetence. Additionally, these precursors acquire self-tolerance, a process that ensures they do not react to self-antigens. This intricate system...
Antigens Involved in Adaptive Immunity01:26

Antigens Involved in Adaptive Immunity

An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and reactivity.
Diversity of Antigen Receptors01:28

Diversity of Antigen Receptors

Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
Antigen Processing Pathways01:31

Antigen Processing Pathways

MHC molecules are key players in the immune response, enabling T cells to recognize and respond to specific antigens. They are present on the surface of all nucleated cells in the body and are instrumental in presenting antigens to T cells and activating them. T cells recognize the MHC-antigen complex and initiate an immune response. MHC class I and MHC class II are two main types of MHC molecules, each associated with a distinct antigen processing pathway.
MHC Class I: Presenting Endogenous...
T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
B Cell Activation and Differentiation01:24

B Cell Activation and Differentiation

The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...

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The Phenotype List String Grammar for Enhanced Protein and Antigen Reporting in the Immunogenetic Context.

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Recommendations for HLA Genotyping Data Standards and Clinical Laboratory Staffing Considerations.

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Maternal-Foetal HLA-DQB1 Incompatibility Is Associated With Pregnancy-Induced Hypertensive Disorders in a Genetically Isolated Population.

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Detection of Human Leukocyte Antigen Biomarkers in Breast Cancer Utilizing Label-free Biosensor Technology
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Repeated local ellipsoid protrusion supplements HLA surface characterization.

Matthias Niemann1, Benedict M Matern1,2, Eric Spierings2,3

  • 1Research and Development, PIRCHE AG, Berlin, Germany.

HLA
|October 19, 2023
PubMed
Summary

We developed Snowball, a new method to predict human leukocyte antigen (HLA) compatibility for kidney transplants. Snowball offers improved sensitivity over existing methods for assessing HLA molecular shape, enhancing graft survival predictions.

Keywords:
HLAdeep neural networkellipsoid fittingmolecular matchingprotrusionstructure prediction

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Area of Science:

  • Immunology
  • Bioinformatics
  • Computational Biology

Background:

  • Donor human leukocyte antigen (HLA) recognition is a key factor impacting long-term kidney transplant success.
  • Current molecular matching algorithms for HLA compatibility have limitations in fully understanding underlying mechanisms.

Purpose of the Study:

  • To develop a more sensitive prediction pipeline, named Snowball, for assessing HLA molecule compatibility.
  • To improve upon the ElliPro approach by iteratively fitting smaller ellipsoids to substructures.

Main Methods:

  • Developed the Snowball pipeline using iterative ellipsoid fitting to HLA substructures.
  • Calculated aggregated protrusion ranks for 712 public and 78 AlphaFold 2-predicted HLA structures.
  • Trained deep neural network predictors using amino acid sequences and protrusion ranks to infer ranks for all known HLA sequences.
  • Implemented a cloud-based web service integrating Snowball's HLA matching capabilities.

Main Results:

  • Snowball demonstrates higher sensitivity than ElliPro in analyzing fine HLA structures, particularly the helix structures of the HLA binding groove.
  • The method is effective when ellipsoids are fitted to substructures within a 15 Å radius.
  • The web service extends the Snowflake pipeline by incorporating protein- and position-specific surface area and protrusion ranks.

Conclusions:

  • The Snowball pipeline provides a more sensitive method for predicting HLA compatibility compared to existing approaches.
  • This advancement can potentially improve the accuracy of predicting kidney graft survival by better characterizing HLA molecular shape and interactions.