Core Concepts-L17- Antigen Recognition by B and T cell Receptors and The Genetics of Lymphocyte Antigen Receptors

what is the basic structure of an antibody? how does this relate to T cells differ/similar?

2 heavy chains and 2 light chains and make a Y- heteroteramers

• N terminal: variable domain- where antigen ends

• C terminal- constant domain- - determines effector function

• antibody- 2 beta pleated sheets held by disulphide bonds

CD8- heterodimer- each chain has 1 Ig domain

CD4- 4 Ig domains

types of MHC classes and genes

1. class I- HLA-A, HLA-B, HLA-C- makes MHC I(CD8)- a1/2/3, b2 micro globulin

2. class II- HLA-DR, HLA-DP, HLA-DQ- makes MHC II(CD4)- a1/2, b1/2

3. TAP1/2, TNF

highly polymorphic!

differences between B and T cell receptors and how they recognise things

TCR

• recognises peptide presented by MHC- explains why MHC restriction is needed

• needs to be chopped by proteasome or acidified in phago-lysosome

• T cell activation and effector function

BCR

• recognises the antigen alone

• doesn’t need MHC presentation

• BCR secretes plasma cells

what is the differences between the antibody responses?

1. primary: first time exposure

• innate: non specific antibodies- IgM and low affinity

2. adaptive/second exposure- IgG- higher levels of antibodies and higher affinity and memory cells

functions of immunoglobulins

1. antigen binding/neutralisation- Fab(variable) region binds specific antigens and neutralise viruses and stops them from infecting cells,

2. agglutination- antibodies with many binding sites can crosslink antigens to make complexes- makes it easier to detect phagocytose. enhances phagocytosis by binding to Fc receptor on macrophages

3. complement activation- Fc triggers complement cascade. Fc binds C1- C3b, opsonisation, C5-C6C9 lysis by MAC formation and amplification of inflammation

discuss roles of Fab and Fc regions- Fc mediated functions(3)

• Fab- antigen binding site and cannot crystallise

• Fc region mediates the effector function

1. Fc receptors on phagocytes- enhances engulfment of antibody coated pathogens

2. NK cell activation- CD16 binds Fc- releases perforin and granzymes

3. complement activation- binds C1-Fc- C3 convertase and C5+C6-C9- opsonisation, C3a/5a- inflammatory mediator

how is antibody specificity and diversity achieved? why can multiple antibodies bind the same protein?

• each antibody can recognise a unique epitope from Fab region- large proteins have many epitopes so many antibodies can bind

• VDJ recombination- for Fab!!!!!!(bone marrow)

• heavy chain by VDJ- DJ then V(Pre B cell)- picks RANDOM D!

• light chain- V-J- VJ (B cell)

• somatic hypermutation- in the VDJ region after antigen activation- germinal centres and gets Tfh- V of heavy and light chain Fab- to get higher affinity

compare IgG and IgM in terms of structure, affinity, function and when they occur

IgM- first exposure

• 10 binding sites

• lower affinity

• low specifcity

IgG- secondary/adaptive

• monomer

• higher affinity

• long term protection and high specificity

what are the forces that hold antibodies and antigens?

• hydrogen bonds

• van der waals

• hydrophobic interactions

difference between affinity and avidity? examples

affinity- strength of one Fab-epitope

avidity- combined strength of ALL Fab sites- IgM in primary has low affinity but high avidity as many are produced

how are antibody types distinguished by eachother?

by the constant region