淋巴细胞基因重排

T Cell Receptor (TCR)

T Cell Receptor (TcR)

•In many ways, the TcR resembles antibody or surface Ig.

•T cells responses are antigen specific.

•Similar to B cells, T cells possess an antigen specific and clonally restricted receptor.

•Genomic organization of TcR gene families and the mechanism of diversity generation of component chains of TcR are similar to B-cell receptor chains.

•Similar to Igαand Ig-βcomplex of B-cell receptor, TcR is associated with a signal–transducing complex, CD3.

T Cell Receptor (TCR)

On the other hand, TCR also differs from B cell receptor (Ig)in many ways.

•TCR is membrane bound and in contrast to B-cell receptor (BCR) (Ig), it does not occur in a soluble form.

•In contrast to BCR, most TCR are not specific to antigen alone rather they are specific to antigen combined with a MHC molecule .

Self–MHC restriction of the TcR •In 1974, Zinkelnagel and Doherty showed that

antigen recognition by T cell is not specific for the antigen alone rather it is specific for the antigen associated with MHC molecule.

•They showed that T cells recognize the antigen only when it is presented by self-MHC molecule.

•This phenomenon,

called ‘self-MHC

restriction’,

differentiates

recognition of antigen

by T cells and B cells.

•Dohorty and

Zinkelnagel were

awarded Nobel Prize

for this work in 1996.

Model for MHC restriction of TCR Two models were proposed

1.The dual receptor model:Two separate TCR;

one for antigen and one for MHC molecule.

2. The altered-self model:Single TCR recognizes

an alteration in self-MHC molecules induced

because of association with foreign antigen.

•Kappler and Marrack showed that specificity for both antigen and MHC molecule resides in

a single receptor.

•At present, ‘altered-self model’is an accepted model for MHC restriction of TCR.

TCR Structure

•Consists of an αand βchain, or a γand δchain.

•In human and mouse, majority of T cells express the αβheterodimer; the remaining T cells (small %) express the γδheterodimer

•No αδ, or γβT cells exist.

•Approximately 105TCR molecules are present on the surface of a T cell.

•Each chain has a variable (V) and a constant domain (C).

•The V domains in both αand βchains contain 3 hypervariable regions which are equivalent to complimentarity determining regions (CDRs) present in Ig light (L)and heavy (H)chains.

TcR Structure

•The βchain also contains fourth hypervariable region but it does not normally contact antigen and is not considered CDR.

•The TCRs are transmembrane, insoluble proteins.

•Transmembrane domains of both chains contain positively charged amino acid residues which play important role in interaction with CD3 complex.

•The most αβTcRs interact with peptide antigens presented by MHC molecules .

TCR Structure

•Certain αβT cells react with nonpeptide

antigens(carbohydrate and lipids) presented by CD1 molecules.

•In contrast to αβTCR, γδ

TCR exhibits limited diversity.

•The γδT cells react with antigen (e.g. phospholipid antigen of Mycobacterium tuberculosis) that is neither processed or presented in the context of a MHC molecule .

TCR is a member of Ig superfamily

•TcR molecule resembles

a Fa

b fragment and is

monovalent.

Diversity of the TCR

•Diversity is achieved by gene rearrangement,

similar to the Ig/Ab molecule.

Ig kappa light chain rearrangement

V and J

rearrangement