Antigen-presenting cells

Concept and classification of APCs

For full activation of a T lymphocyte, antigen recognition alone is not enough. A second signal is required — costimulation, which is mediated through the interaction of additional surface molecules (e.g., B7/CD80, CD86). A cell bearing MHC class I and II complexes on its membrane in combination with costimulatory molecules is theoretically an antigen-presenting cell.

In immunology, APCs are divided into two main groups:

• "Professional" APCs: dendritic cells, macrophages, and B lymphocytes. Their main task is presenting antigens to T cells.
• Non-professional APCs: other body cells (epithelial, endothelial, etc.) that do not present antigens under normal conditions, but are capable of acquiring such properties during inflammation and activation.

Comparison of professional APCs

The three main types of professional APCs differ in their mode of antigen uptake, surface molecule expression, and ability to activate different T-lymphocyte subpopulations.

Note: MHC-I and MHC-II molecules are present in all three cell types.

Primary immune response and the role of dendritic cells

When the body encounters an antigen for the first time, the immune response must start with the activation of naive T lymphocytes. This task can be performed only by dendritic cells, because their antigen-presenting capacity is approximately 100 times higher than that of macrophages.

The initiation of the primary response relies on the interaction between dendritic cells and CD4+ T helper cells. This contact not only initiates the reaction but also serves as the main bridge between the innate (dendritic cells) and adaptive (T helper cells) branches of immunity.

Clonal organization and presentation paradoxes

The T-lymphocyte population is organized clonally: each individual cell carries a unique T-cell receptor (TCR) that recognizes strictly one antigenic pattern. During antigen presentation, the immune system faces two major quantitative hurdles:

1. Critical shortage of specific T lymphocytes.

There are very few cells of the required clone in the regional lymph node. For example, in mice, the total number of TCR variants exceeds 500,000, while a single lymph node may contain fewer than 10 cells capable of recognizing a specific antigen. The probability of their physical encounter with a dendritic cell is extremely low.

1. Deficiency of antigenic complexes on the APC membrane.

To activate a T helper cell, its receptors must bind to 200–500 MHC-II molecules bearing the required peptide. However, a dendritic cell simultaneously presents many different proteins, and the target antigen accounts for no more than 0.1% (about 30–100 molecules per cell). This is significantly lower than the threshold required for activation.

Despite these mathematical contradictions, the immune system successfully overcomes these barriers through specialized mechanisms that ensure efficient search and activation of cells.

Class and exam questions

What else to study on this topic

• Mechanisms for overcoming the quantitative deficiency of T-lymphocyte clones.
• Antigen processing and assembly of MHC-peptide complexes inside the cell.
• The role of B7 family costimulatory molecules (CD80/86) and their receptors.
• Features of the activation of memory cells and effector lymphocytes.

Other topics in the "Adaptive Immunity" section

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