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Related Concept Videos

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...
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.
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...
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...
Special Features of Adaptive Immunity01:20

Special Features of Adaptive Immunity

The adaptive immune system, a crucial component of the overall immune response, offers a highly specialized defense against pathogens. It involves specific cell types and features, enabling it to combat infections effectively and efficiently.
The primary cell types involved in adaptive immunity are T cells and B cells. Each type has a unique role in defending the body against pathogens. T cells are responsible for cell-mediated immunity. They identify and eliminate infected cells directly,...
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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Structural features underlying T-cell receptor sensitivity to concealed MHC class I micropolymorphisms.

Guillaume B Stewart-Jones1, Peter Simpson, P Anton van der Merwe

  • 1Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, United Kingdom.

Proceedings of the National Academy of Sciences of the United States of America
|November 20, 2012
PubMed
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Subtle differences in human leukocyte antigen (HLA) class I subtypes can alter T-cell receptor (TCR) interactions. This impacts immune responses to HIV-1, influencing disease outcomes.

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Area of Science:

  • Immunology
  • Structural Biology
  • Molecular Medicine

Background:

  • Polymorphisms in Major Histocompatibility Complex (MHC) class I molecules influence T-cell repertoire selection and disease susceptibility.
  • The precise molecular mechanisms by which subtle MHC class I variations impact T-cell receptor (TCR) interactions and downstream cellular functions remain incompletely understood.

Purpose of the Study:

  • To investigate the structural and functional consequences of minor polymorphisms in HLA-B*57 subtypes on T-cell receptor binding and activation.
  • To elucidate the molecular basis for differential T-cell responses to HIV-1 epitopes presented by HLA-B*5701 versus HLA-B*5703.

Main Methods:

  • Structural analysis of MHC-peptide-TCR complexes.
  • Thermodynamic measurements of binding affinities and kinetics.
  • Functional assays assessing T-cell activation and expansion.

Main Results:

  • Both HLA-B*5701 and HLA-B*5703 present the conserved HIV-1 epitope in structurally similar formats.
  • Differences in TCR binding kinetics and cellular function arise from subtle peptide adjustments during TCR ligation, influenced by polymorphic residues and water molecules.
  • A conserved TCR specific for the HIV-1 epitope is expanded by HLA-B*5701 but not by HLA-B*5703.

Conclusions:

  • Minor MHC class I micropolymorphisms can significantly impact TCR usage and binding kinetics through peptide-MHC interactions.
  • These subtle structural variations have implications for differential immune responses and disease outcomes in viral infections and autoimmune conditions.