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Antigen recognition by T cells Zheng W. Chen, M.D., Ph.D

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 a chain and TCR b chain. ab TCR heterodimers are very similar in structure to a Fab fragment of

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Antigen recognition by T cells Zheng W. Chen, M.D., Ph.D

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  1. Antigen recognition by T cells Zheng W. Chen, M.D., Ph.D

  2. T cell receptors (TCR) on T cells recognize antigens TCR is a heterodimer comprised of 2 transmembrane glycoprotein chains; TCR a chain and TCR b chain. ab 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 ab TCR heterodimers; a minority of T cells express another type of TCR, gd TCR heterodimers. CDR loops of TCR form the antigen- binding sites. Theoretically, each T cell expresses a unique TCR in terms of VDJ sequences.

  3. T cell receptor ab heterodimers

  4. TCR CDR loops form the antigen-binding sites

  5. 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”).

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

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

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

  9. 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).

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

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

  12. TCR binds to the MHC:peptide complex

  13. New studies from my lab and others have shown that human and higher primate gd T cells can recognize nonpeptide phosphoantigen from mycobacteria (shen et al, Science 2002) ab T cells gd T cells ??? APC presenting cells Ag presentation MHC ??? peptide phosphoAg ab TCR gd TCR

  14. Phosphoantigen-specific gd T cells expressing Vg2Vd2 TCR can undergo major clonal expansion in mycobacterial infection. (Shen et al, Science; Chen et al, Trends Immunol, 2003).

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