Immunology test 3

· CD4 T cells (aka helper T cells) have the co-receptor CD4 on their surface and recognize antigen bound to MHC class II.

· CD8 T cells (aka killer T cells) have the co-receptor CD8 on their surface and recognize antigen bout to MHC class I.

How do T cells recognize antigen? 

· Via a T-cell receptor (TCR) 

· A highly variable antigen-specific receptor 

· Recognize mainly protein antigens bound to a human glycoprotein (aka MHC) 

· Have similarities and differences to Immunoglobulin.

· Fig. 5.1 shows the structural difference between Ig and a TCR

· The T cell receptor consist of two separate chains (alpha and beta or gamma and delta  (Fig. 5.7) 

· There are actually two types of T cells based on TCR. We will focus primarily on α: β T cells because they are the primary T cells in circulation for most vertebrates. 

· A few points to know about γ:δ T-cells: 

1. They are more abundant in tissues compared to circulation 

2. Behave differently from α: β T cells in that they can have effector functions 

3. Antigen recognition is not dependent on antigen presentation in MHC 

· Each chain has four basic parts 

1. A cytoplasmic tail 

2. A transmembrane region 

3. A constant region 

4. A Variable region 

· A genomic recombination event (similar to that of somatic recombination in B cells) allows for variation in antigenic binding sites of T cells. (Fig. 5.3) 

· You are not responsible for knowing this process in detail, but definitely know that it occurs.

· T-cell receptors form a T cell receptor complex with CD3 proteins (Fig. 5.6) 

· A T cell receptor can recognize antigen but alone it is not going to be able to transduce a signal when antigen is bound. 

· T-cell receptors can have major functions when activated by antigen (Fig. 5.13).

· Kill sick cells. (CD8 T cells)

· Send cytokine signals to activate macrophages. (CD4 T cells)

· Send cytokine signals to activate differentiation and further cell division of activated B cells. (CD4 T cells)

What are MHC molecules? 

· MHC stands for major histocompatibility complex.  

· Present peptide (protein) antigens to T cells.  

· Antigen is processed within a cell, bound to MHC and then the MHC with antigen is inserted into the cytoplasmic membrane. Only then can a T cell recognize antigen within a MHC molecule. Refer to Fig. 5.10 

· There are two types of MHC. 

· Refer to Fig. 5.11:   MHC class I and MHC class II 

· MHC (HLA) class I  

· Expressed by a broad range of cell types (Fig. 5.25) 

· Presents antigen from intracellular pathogens (Fig. 5.27) for example viruses. 

· Binds short fragments of peptides from the intracellular pathogens (8-10 amino acids in length). 

· Exhibits  promiscuous biding specificity  

· Can bind thousands of peptides with different amino acids sequences 

· Presents antigen to CD8 T-cells (Fig. 5.15) 

· MHC (HLA) class II 

· Expressed by a limited number of cell types (Fig. 5.25) 

· Presents antigen from extracellular pathogens (Fig. 5.27). ie. most bacteria 

· Binds large fragments of peptide (usually 13 to 25 amino acids in length) 

· Exhibits promiscuous biding specificity 

· Presents antigen to CD4 T-cells (Fig. 5.15) 

· MHC molecules are encoded within the major histocompatibility complex 

· The major histocompatibility complex 

· According to your book, the major histocompatibility complex (MHC) is a large cluster of mainly immune-system genes present in all vertebrates that encode MHC molecules. Fig. 5.30  

· In humans, it is referred to as the  human leukocyte antigen complex (HLA)   

· Human MHC molecules are called HLA class I and II molecules. 

· MHC (HLA) molecules  

· The basis of an individual’s tissue type. 

· There is inherited diversity in HLA types between individuals.  

· This diversity is not as great as for a TCR or Ig it is still very important for antigen binding and presentation as well as tissue rejection. 

· Unlike B and T cell receptors, the diversity of HLA types is not a product of any type of genomic rearrangement. 

· This diversity arises from  two sources : 

· 1.  The presence of gene families  

· There are multiple similar genes encoding the MHC class I and class II proteins. 

· Protein products from these gene families are referred to as isotypes. Fig. 5.28 

· Each isotype has a particular functions: 

· HLA-A, HLA-B and HLA-C present antigen to CD8 T cells and NK cells 

· HLA-E and HLA-G present antigen to NK cells 

· HLA-F function is unknown 

· HLA-DP, HLA-DQ and HLA-DR present antigen to CD4 t cells HLA-DM and HLA-DO help to load antigen onto the other 3. 

· 2.  Genetic polymorphism  

· The presence within the population of multiple alternative forms of a gene or alleles.  

· Different MHC isotypes display varying levels of polymorphisms 

· Highly polymorphic human MHC isotypes have multiple alleles circulating within a population whereas less polymorphic isotypes have less alleles circulating within a population (Fig. 5.28).