Ags Ag Receptors Lecture B BMS2045 2025

Antigens and Antigen Receptors

Presented by Dr. Natalie Riddell (n.riddell@surrey.ac.uk)

Theme 3 Discussion Board

Lecture Overview

• Lecture A: General Principles, Antigens, Immunogens, B cell receptor (BCR), and Antibodies.

• Lecture B (Wednesday 10am): Epitopes, Affinity, Avidity, T cell receptor (TCR), Polyclonal responses.

• Lecture C (Thursday 2pm): MHC Class I & II, antigen processing, presentation, and genetics of antigen recognition.

Epitopes

• Definition: Specific parts of an antigen that bind to antibodies or T cell receptors, crucial for identifying pathogens.

• Antibodies recognize unique epitopes on antigens, determining the specificity of the immune response.

• Epitopes can be categorized into two types:

  • Linear Epitopes: Composed of continuous amino acid sequences.

  • Discontinuous Epitopes: Formed from non-contiguous regions of the protein, bringing together different parts of the sequence upon folding.

Immunoglobulin-Antigen Interactions

Definitions

• Paratope: The specific region on an antibody that binds to an epitope, offering precision in targeting antigens.

• Binding Mechanics: Effective binding requires a perfect fit between the epitope and the paratope, influenced by molecular shapes and charges.

• Complementarity Determining Regions (CDRs): These are hypervariable regions on the antibody that significantly contribute to the binding site structure, synthesized from both heavy (VH) and light chains (VL).

• Affinity and Avidity: Stronger binding correlates with higher affinity, which is the measure of how tightly an antibody binds to a single antigenic determinant; higher affinity antibodies can effectively operate at lower concentrations.

Antibody Characteristics

• Affinity: Represents the strength of binding between an antibody and a single antigenic determinant. High affinity antibodies are typically effective at lower concentrations during immune response.

• Avidity: Refers to the total strength of binding from multiple antibody-antigen interactions, which is influenced by the number of binding sites available on the antibody and the number of epitopes on the antigen.

• IgM Antibodies: Characterized by low affinity due to their structure, but possess high avidity as they can bind multiple antigens through their pentameric form, allowing them to aggregate pathogens effectively during the initial immune response.

B Cell Receptors (BCRs)

• Role and Function: Antibodies are secreted forms of BCRs; each individual B cell can produce distinct antibodies tailored to specific antigens.

• Class-Specificity: B cells have five subclasses differentiated by their function and structure: IgM (first responder), IgA (mucosal immunity), IgE (allergic reactions), IgG (primary for long-term immunity), and IgD (exact function still under investigation). IgM is typically predominant in the initial immune response due to its structure allowing for effective antigen clustering.

T Cell Receptor (TCR) and Immunology

Structure and Function

• Similarities with BCRs: TCRs are structurally similar to the Fab fragments of BCRs, consisting of two different peptide chains.

• Domains: Each TCR contains variable and constant regions, allowing diversification to recognize a wide variety of antigens; types include αβ and γδ TCRs.

• Signalling Requirement: TCR requires the CD3 complex for effective signaling, which is made up of several polypeptides that assist in T cell activation and proliferation.

• Antigen Recognition: T cells primarily recognize peptides presented by Major Histocompatibility Complex (MHC) molecules, with CD8 T cells specifically binding to MHC Class I and CD4 T cells to MHC Class II.

Antigen Presentation

• Activation of T Cells: For T cell activation, antigens must be processed and presented by Antigen Presenting Cells (APCs), such as dendritic cells, macrophages, and B cells.

• Superantigens: A unique class of antigens that can bypass normal processing pathways, activating a large proportion of T-helper cells directly, leading to a robust but often uncontrolled immune response.

TCR Variants and Immune Specificity

• Each TCR is unique, enabling highly specific binding to anticipated antigens, but requires MHC presentation for recognition.

• γδ T cells: Distinct in their function and capable of recognizing non-peptide antigens presented by CD1 molecules, diverging from the classical MHC-dependent pathways.

Polyclonal Responses

• Infection Response: Polyclonal responses occur during infections when different clones of T and B cells proliferate to recognize various antigens rapidly.

• Monoclonal Antibodies: Derived from a single clone, these antibodies recognize one specific epitope and are utilized in various diagnostics and therapeutics.

• Polyclonal Antibodies: Composed of antibodies from multiple clones, these can recognize different epitopes, providing a more versatile immune response.

Summary of Similarities and Differences in BCRs and TCRs

• Both BCRs and TCRs share immunoglobulin fold structures, constant and variable regions, and necessitate accessory proteins for signaling. However, they differ in signaling properties, the number of binding sites, and whether they exist in soluble or membrane-bound forms.

Upcoming Topics

• The next lecture will delve deeper into antigen presentation mechanisms utilizing MHC I & II and explore the genetics behind antigen recognition, which is crucial for understanding immune system specificity and response dynamics.