Antigen recognition by T cells

Zheng W. Chen, M.D., Ph.D

T cell receptors (TCR) on T cells recognize antigens

TCR is a heterodimer comprised of 2

transmembrane glycoprotein chains;

TCR chain and TCR chain.

TCR heterodimers are very similar

in structure to a Fab fragment of

immunoglobulin, bearing V, (D), J, C

segments.

A majority of T cells express TCR

heterodimers; a minority of T cells

express another type of TCR, TCR

heterodimers.

CDR loops of TCR form the antigen-

binding sites.

Theoretically, each T cell expresses a

unique TCR in terms of VDJ sequences.

T cell receptor heterodimers

TCR CDR loops form the antigen-binding sites

TCR recognize antigen peptide presented by a MHC molecule

TCR recognition of antigen differs from antibody recognition of antigen (TCR cannot bind directly to an antigen peptide).

Ag peptide must be presented by a corresponding MHC molecule before TCR can recognize.

TCR interact with the peptide-MHC complex (ligand) by making contact with both the antigen peptide and the MHC (“Dual recognition”).

Class I is comprised of one transmembrane glycoprotein ( chain) and a 2- microglobulin; Class II are dimmers of and transmembrane glycoproteins

CD4 T cell recognize antigen peptides bound to MHC class II molecules; CD8 T cells recognize

antigen peptides bound to MHC class I molecules.

Historically, T cell (TCR) recognition of antigen peptides were characterized by antigen peptide stimulation assays in culture:

CD4 T cells + specific Ag peptide Interleukin 2 (IL-2)APC or Interferon (IFN-)

CD8 T cells + specific Ag peptide cytotoxic killing of target cells(target cells) APC or production of IFN-

Why CD4 T cells recognize peptide/MHC class II and CD8 T cells see peptide/MHC class I ?

CD4+ T cells CD8+ T cells

Antigen presenting cells (APC) and expression of MHC class I and II molecules Professional APC: macraphages/monocytes/Langerhams cells; dendritic cells, B cells, express both MHC class II and I. In general, all tissue cells can express Class I; but not Class II (endothelial cells can express both).

Class I molecules bind short peptides of 8-10 amino acids by both ends (binding sites for anchor residues of a given peptide).

MHC Class II molecules bind 12-15 AA or longer peptides

TCR binds to the MHC:peptide complex

New studies from my lab and others have shown that human and higher primate T cells can recognize nonpeptide phosphoantigen

from mycobacteria (shen et al, Science 2002)

TCR

???

presenting cells

Ag presentation

TCR

peptide

MHC

APC

phosphoAg

???

T cells T cells

Phosphoantigen-specific T cells expressing V2V2 TCR can undergo major clonal expansion in mycobacterial infection. (Shen et al, Science; Chen et al, Trends Immunol, 2003).

0.6 0.3

0.3

0.4 23.4

0.6

Anti-V2-FITC

Ant

i-V2

-PE

Week 0 Week 3