T -CELL RECEPTORS

T -CELL RECEPTORS FOR ANTIGEN

v  In mature individuals development of T cell in thymus slow down and T-cell numbers  are maintained through division of mature T cells outside of the central lymphoid organs

v  (B cells are continuously produced from bone marrow even in adults)

T-cell receptor exists as a heterodimer- there are 2 types—

v  α and β chain (α β-TCR) 

v  γ and δ chain  (γδ-TCR)  

v   αβ TCR – reffered to as αβ T cell

 

 

structure and Function of αβ T cell

•       


•       α-chain(43-49kDa)

•       β-chain (38 - 44kDa)

•       The variable and constant domain  follow the nomenclature of immunoglobulin molecules Vα, Vβ, Cα and Cβ

•       There are hyper variable regions of the variable domain forming CDRs 1-3

•       Function

•       Recognize and bind the antigen or (shape formed by the peptide embedded within an MHC molecule groove).

Function

•       CDRs 1 and 2 interact with 2 α -helices of the α1 and α2 domains of MHC molecule, as these run along the sides of the antigen binding groove

•       CDR3 interacts with the peptide within the groove

•       CDR -Complementarity determining regions

 

Chains of each type of TCR are divided into:

•        1. Variable domain   2. Constant domain

v  T-cell expresses only one form of TCR once genes have been rearranged

v  γδTCR appear on surface of primitive T lymphocytes in thymus b4 αβ TCR can be seen hence TCR1(γδ) and  TCR2(α β)

v  however TCR2(α β) remains the best studied in human and is present in over 90% of peripheral T-cells (1-10% for  TCR1(γδ))

v  αβ T cells –much more is known on its antigen responsiveness, while γδT cell is still not clear

 

Genes of  α chain

v  Αn α chain is formed by recombination of segments from different gene groups, in this case

v  V α (50-100),

v  Jα (50 -100)

v  Cα(1),

v  diversity achievable for α chain –

    100 x 100x1= 10,000

 

Genes of β chain gene

v  β chain gene consists of Vβ , Dβ,  Jβ and  Cβ,

v  Vβ (50-100),

v  Dβ (2),

v  Jβ (12),

v  Cβ (2),

v  Potential diversity of gene segment—100x2x12x2 =48,000

v  Overall diversity achievable from a set of α and β chain gene rearranging and producing polypeptide chains   4800x10, 000=48 million

Genes of  γ chain

v  Human γ chain gene segment contains 3 gene segment –

v  V -8,

v   J- 2,

v  C-2 

v  Diversity achievable 8x2x2 = 32 diff. rearranged genes

 

 Genes of δ chain

v  δ chain genes are located within the middle of the chain gene locus and are arranged in four pools of

v   V(10 genes),

v  D(2 genes),

v  J( 3 genes) and

v  C(1 gene)

v  Potential diversity: 10x2x3x1=60 possible rearranged combined with the chain genes total diversity in the receptor 32x60 =1920

 


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