Immunology for Non-Immunologists: T Cell Antigen Recognition

Our new series, Immunology for Non-Immunologists, will focus on key concepts to help scientists and researchers without extensive immunology backgrounds understand the functions and use cases for our immune cell products.

This post focuses on the T cell antigen recognition process. If you have other questions about using our products in your lab, just ask one of our scientists! No question is too big or too small; we’re here to help!

How T Cells Recognize Antigens

Breaking Down the Process

You probably already know the basic premise of the immune response to foreign bodies: Antigens enter the body, triggering the immune response and release of antibodies, which bind to specific antigens by interacting with their three-dimensional surface.

T cells also play an important role in adaptive immunity, but unlike antibodies, T cells cannot bind directly to antigens. So what do T cells recognize?

T cells have dual specificity, so they recognize both self-major histocompatibility complex molecules (MHC I or MHC II) and peptide antigens displayed by those MHC molecules. The receptors on these T cells recognize a linear, two-dimensional peptide sequence (between 8 to 12 amino acids in length) from the antigen bound to the MHC molecules expressed on the surface of the antigen-presenting cells.

So the T cell receptor actually recognizes this combination of the MHC molecule and the peptide. Once bound to the MHC molecule, the T cell can begin its role in the immune response.

Astarte Blog 53018

Bailey, A. et al. Selector function of MHC I molecules is determined by protein plasticity. Sci. Rep. 5, 14928; doi: 10.1038/srep14928 (2015).

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Disrupting the Reception

If anything in this process changes, such as a change of the MHC molecule or change in the amino acid in the peptide antigen, the T cell receptor may fail to recognize the antigen, which can compromise the immune response.

The T cell receptor tolerates some changes, so recognition can be successful. Other changes are not tolerated and disrupt the recognition process or alter the activation.

For example, our HPV-specific T cells recognize a peptide from the E7 protein of the human papillomavirus (HPV). The sequence is YMLDLQPETT. If the sequence is short one amino acid to YMLDLQPET, the T cells do not recognize it.

On the other hand, we generated our MBP-specific T cells by stimulating PBMC with the sequence ENPVVHFFKNIVTPRTP from myelin basic protein (MBP). They also recognize an overlapping sequence of FFKNIVTPRTPPPSQGK. Given their ability to recognize both of these sequences, the amino acids ENPVVH are not needed nor is the PPSQGK on the carboxy end. The core sequence recognized is within FFKNIVTPRTP.

What This Means for Your Research

Antigen-specific T cells are vital to the study of immunological and inflammatory responses to bacteria, viruses, cancers, and other pathogens. Understanding the basic function of the T cell recognition process will help you design and execute more fruitful experiments.

We have T cells that recognize peptide antigens from CMV, HPV, influenza, tetanus toxoid, and myelin basic protein, and we’re developing others as well. We can also source custom T cells specific to your antigen of interest.

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2 thoughts on “Immunology for Non-Immunologists: T Cell Antigen Recognition

  1. Grammatiki says:

    Hello Anne,

    you say that:
    “For example, our HPV-specific T cells recognize a peptide from the E7 protein of the human papillomavirus (HPV). The sequence is YMLDLQPETT. If the sequence is short one amino acid to YMLDLQPET, the T cells do not recognize it.”

    How do you know this? I am currently trying to find out what is the difference between these two epitopes and I came across several publications that say the 9-mer is actually inducing more potent immune responses than the 10-mer.

    doi: 10.1074/jbc.M110.126722
    doi: 10.3389/fimmu.2011.00075

    Best wishes,
    Grammatiki.

    • Anne Lodge says:

      Hi Grammatiki, Thanks for your post. We can detect robust production of IFNg from the HPV E7-specific T cells when the target cells are pulsed with the 11-20 peptide but do not respond to the 11-19 peptide or any other HLA-A2 binding peptide. So I’m confident these two epitopes are not cross reactive. I am aware that there are publications on both sides of this question (11-19 vs 11-20). We tried to generate T cell lines using the 11-19 without success but we were able to generate T cells reactive to 11-20. We haven’t tried to use the peptides in parallel with PBMC from the same individual. That would be a way to directly compare the two. But we were just interested in generating an HPV specific T cell line, not in a direct comparison of the two epitopes. It is surprising that one amino acid makes such a difference but I suspect those terminal threonines are binding to the P9 pocket and the added threonine results in the peptide bulging out in a way that is important for T cell recognition.

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