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Immunology · Adaptive Immunity

Molecular immunology

Immunologia molecularis

Molecular immunology studies cellular receptors, antigenic determinants, and the mechanisms of recognizing "self versus non-self". The discipline is based on Burnet's clonal selection theory and the discovery of the major histocompatibility complex.

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Discovery of the MHCThe major histocompatibility complex forms the basis of transplantation immunity.
Clonal Selection1 lymphocyte clone recognizes 1 specific antigen epitope.
EpitopesRegions of an antigen molecule that interact with receptors and antibodies.
BCR ReceptorsInclude membrane immunoglobulin, CD19 and CD21 coreceptors, and signaling chains.
2 min readFor medical studentsUpdated 10.10.2026
Material prepared by WhiteCoat Pro editorial team based on platform study guidesPending instructor review

Evolution of theories and the clonal selection concept

In the 1930s, erroneous "instructive" theories dominated, suggesting that the antigen itself shaped the antibody conformation. Modern science relies on the clonal selection theory by F.M. Burnet and J. Lederberg (1957). According to this theory, lymphocyte clones with pre-existing receptors for all epitopes already exist in the body.

The fate of a lymphocyte depends on its maturity:

  • Insufficiently mature cells die upon contact with an antigen, eliminating clones directed against self-tissues.
  • Mature lymphocytes trigger proliferation and differentiate into effector cells upon encountering foreign structures.

Specificity and structure of antigenic determinants

The interaction of immune molecules occurs not with the entire surface of the captured agent, but with its localized regions — epitopes. In complex proteins, there is a hierarchy of such regions: one of them is dominant (immunodominance), and it is primarily against this region that the bulk of antibodies is synthesized.

Different classes of antigens have their own distinct features:

  • Polysaccharides contain repeating uniform epitopes.
  • Proteins differ in structural diversity, with individual antibodies produced against each of them.
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Structure of the B-cell receptor (BCR)

The BCR complex ensures the recognition of foreign substances and initiates the intrinsic response of the lymphocyte. It consists of several functional components:

  1. The BCR proper — membrane immunoglobulin (mIg).
  2. Signaling molecules — Igα and Igβ (CD79) heterodimers, which transmit signals inside the cell via tyrosine kinases.
  3. The coreceptor complex — includes CD19 (associated with the lipid kinase PI3K), CD21 (CR2, complement receptor), and the tetraspanin CD81.

An array of kinases (Fyn, Blk, Lyn, Lck, Syk) is involved in activating these processes, providing a signal transduction cascade.

Immunological tolerance and T-independent responses

Immunological tolerance was discovered by P. Medawar and represents an active suppression of the response to a specific agent. It develops during ontogenesis if the substance enters the body before the immune system matures.

Features of responses to T-independent (TI) antigens:

  • Isotype switching is absent (the main class is IgM) along with affinity maturation.
  • A full-fledged immunological memory does not form.
  • B-cell activation occurs due to receptor clustering at high epitope density or with the participation of pattern recognition receptors (TLR-4).
How to memorize

"One clone — one epitope": the rule of Burnet's clonal selection theory.

Class and exam questions

What is the essence of the clonal selection theory?

Lymphocyte clones bearing receptors for all possible epitopes are spontaneously generated in the body. The antigen does not "teach" the cell to build an antibody from scratch, but merely selects and stimulates an already prepared complementary clone.

What is the immunodominance of protein antigens?

This is the hierarchy of epitopes in a protein molecule where one region is dominant — the largest number of antibodies is produced against it. If this epitope is removed, dominance shifts to the next one in the hierarchy.

What components are part of the BCR coreceptor complex?

The B-cell receptor coreceptor complex includes membrane molecules CD19, CD21 (complement receptor CR2), and tetraspanin CD81, which enhance the activation signal.

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What else to study on this topic

  • History of discovery and structure of the T-cell receptor (TCR)
  • Differences between TI-1 and TI-2 antigens during B-lymphocyte activation
  • Factors determining the choice between immunogenicity and tolerogenicity
  • The role of cytokines (IL-10, IL-12, IFNγ) in regulating the immune response
  • J. Miller's discovery of the thymus's role and lymphocyte heterogeneity

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Other topics in the "Adaptive Immunity" section

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