Antigen Presentation to Lymphocytes

Abstract

Antigen presentation to T and B lymphocytes by antigen‐presenting cells plays a central role in the initiation and regulation of adaptive immune responses. T cells recognise peptides in the context of major histocompatibility complex (MHC) molecules via T cell receptors (TCRs). In contrast, B cells recognise and bind proteins via membrane‐bound immunoglobulins, known as B cell receptors (BCRs). Which epitopes are recognised by TCRs and BCRs has a major impact on the cell‐mediated immune response.

Key Concepts

  • T lymphocytes are key players in the adaptive immune response.
  • T lymphocytes need professional antigen‐presenting cells (APCs) to be primed.
  • Upon priming, T cell activation does not need professional APCs.
  • CD8+ T cells mediate the cytotoxic response against infected cells.
  • CD8+ T cells can mediate the cytotoxic response against cancer cells.
  • T cell receptor αβ (TCR αβ) recognises complexes formed by major histocompatibility complex (MHC) molecules and antigenic peptides.
  • After several steps of the antigen processing and presentation (APP) pathway, antigenic peptides are presented by MHC molecules to T cells.
  • An antigenic peptide that triggers a T cell activation is defined as an ‘epitope’.
  • Unconventional epitopes such as posttranslationally spliced epitopes can trigger a T cell response.

Keywords: T cell; B cell; dendritic cell (DC); MHC class I; MHC class II; antigenic peptide; antigen processing and presentation

Figure 1. Antigen presentation to T lymphocytes. (a) CD8+ cytotoxic T cells recognise antigenic peptides presented by class I major histocompatibility complex (MHC) molecules. (b) CD4+ helper T cells recognise antigenic peptides presented by class II MHC molecules.
Figure 2. Processing of endogenous and exogenous proteins into peptides for loading onto MHC molecules. Proteins are often poly‐ubiquitinylated by ubiquitin‐specific activating enzyme (E1), conjugating enzyme (E2) and ubiquitin ligase (E3) prior to their degradation catalysed by the 26S–30S proteasome, although poly‐ubiquitin‐independent pathways have been described. Some of these degraded peptide products are then loaded onto MHC class I molecules in the ER and transported to the cell surface. On the other hand, internalised exogenous proteins or even endogenous proteins engulfed by autophagosomes are transported into the endosome/MIIC compartment and degraded by acid proteases. The produced peptides are loaded onto MHC class II molecules that have been escorted by the invariant chain (Ii) to the MIIC compartment. Udono . Reproduced with permission of John Wiley & Sons.
Figure 3. Proteasome structure and peptide splicing. (a) The human 20S core particle of the proteasome is shown based on the structure generated by (Schrader et al., ). Some of the proteasome subunit chains are hidden from the structure in order to see the inner proteasome cavities with the central chamber and its two antechambers. The α and β subunits are coloured in grey and blue, respectively. As an example of a catalytic subunit, the β2 subunit is shown in pink with its active site threonine in red. (b) Posttranslationally spliced peptides can be formed by i. cis peptide splicing, when the two splice‐reactants derive from the same polypeptide molecule; the ligation can occur in normal order, that is, following the orientation from N‐ to C‐terminus of the parental protein (normal cis peptide splicing), or in the reverse order (reverse cis peptide splicing); ii. trans peptides splicing, when the two splice‐reactants originate from two distinct protein molecules or two distinct proteins.
Figure 4. Antigen presentation to B lymphocytes by follicular dendritic cells (FDCs) in a germinal centre. B cells undergo rapid proliferation accompanied by somatic hypermutation in their rearranged immunoglobulin genes, resulting in the generation of both antigen‐specific high‐affinity B cells and B cells that no longer recognise the antigen. High‐affinity B cells that recognise antigens presented by FDCs survive and differentiate, with the help of T cells, into either memory or plasma (antibody‐secreting) cells. In contrast, B cells that no longer recognise the antigen die through programmed cell death (apoptosis). Udono . Reproduced with permission of John Wiley & Sons.
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Further Reading

Sompayrac LM (2019) How the Immune System Works, 5th edn. Wiley‐Blackwell. ISBN: 978‐1‐118‐99777‐2.

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Muharemagic, Darija, Scott, William, and Mishto, Michele(Oct 2019) Antigen Presentation to Lymphocytes. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001227.pub3]