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Antigen recognition by T-cells

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Q&A: How do T-cells recognize antigens?

Author: Sanketh DS, MDS

T lymphocytes cannot directly recognize or be activated by antigens on microbes or those that are extra-cellular in circulation. They are rather programmed to be able to recognize antigens that are presented to it by antigen presenting cells like B lymphocytes, macrophages, dendritic cells or other nucleated cells. Very specifically, T-cells require peptides derived from these antigens to be presented along with certain cell surface molecules called MHC molecules.

T-lymphocyte possesses a T cell receptor made of an αβ polypeptide chain which recognizes peptides displayed by the MHC molecule. Apart from the TCR, T cells also possess other proteins and co-receptors that are necessary for signal transduction for T-cell activation after antigen recognition. CD4 and CD 8 molecules are co-receptors present on CD4+ and CD8+ T cells respectively. These co-receptors bind to the MHC molecule during antigen recognition and are necessary for T-cell activation. CD 3 complex are a bunch of polypeptides that help in transduction of signals for T-cell activation and CD-28 is a co-receptor that binds to a B7 molecule present on the nucleated or antigen presenting cell.

MHC molecules are proteins encoded by MHC genes located in the short arm of chromosome 6. There are 3 types of MHC molecules MHC I, II and III out of which I and II are important for antigen recognition by T-cells. In fact, their function is to display peptides on the cell surface of an antigen presenting or a nucleated cell, for the purpose of recognition by T-cells.


An endogenous antigen like a virus or a tumor antigen is broken down into peptides by proteasomes inside the cell and are transported to the endoplasmic reticulum. Here, the MHC I molecule captures the peptide, and is then transported to the plasma membrane, where it displays the peptide on the cell surface, ready for recognition. Peptide bound MHC I molecule is recognized by a CD 8+ T cell –  the TCR interacting with the peptide and the CD 8 co-receptor binding with the MHC I molecule. CD 8+ T cells are MHC class I restricted and can recognize peptides only bound with MHC I molecule.


An exogenous antigen, captured by an APC like a dendritic cell or a macrophage undergoes proteolytic degradation in lysosomes, and the broken down peptides bind to class II MHC in the lysosome. The peptide bound MHC II is transported to the cell surface, and is subsequently recognized by a CD 4+ T cell – the TCR interacting with the peptide and the CD 4 co-receptor binding with the MHC II molecule. CD 4+ T cells are MHC class II restricted and can recognize peptides only bound with MHC II molecule.


Kumar V, Abbas AK, Fausto N, Aster JC. Robbins and Cotran – Pathologic Basis of Disease. 8th Edition. Saunders Elsevier; 2010.

Abbas AK, Litchman AH, Pillai S. Cellular and Molecular Immunology. 8th Edition. Saunders Elsevier; 2015.


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