Clonal deletion
In
Discovery and function
Location
B and T lymphocytes are tested for their affinity for self
B cells
B cells demonstrating high affinity for self antigen can undergo clonal deletion within the bone marrow.[1][3] This occurs after the functional B-cell receptor (BCR) is assembled.[1] It is possible for B cells with high self affinity to go undeleted because they require activation signals and stimulation from autoreactive T cells. Such T cells are often removed via clonal deletion, leaving autoreactive B cells unstimulated and unactivated.[1] These B cells do not pose a threat, even in the periphery, because they cannot be activated without an autoreactive T cell to stimulate them.
T cells
Between 2% and 5% of T cells develop auto-reactive receptors. Most of these undergo negative selection by clonal deletion.[1]
Thymic cortex
T cells that show a high affinity for self MHC/peptide complexes can undergo clonal deletion in the thymus.[1][3] Thymic dendritic cells and macrophages appear to be responsible for the apoptotic signals sent to autoreactive T cells in the thymic cortex.[1][6]
Thymic medulla
T cells also have the opportunity to undergo clonal deletion within the thymic medulla if they express high affinity for self MHC/peptide complexes. This helps eliminate autoreactive T cells that recognize a protein from a specific body part.
Complete vs. incomplete clonal deletion
Complete clonal deletion results in apoptosis of all B and T lymphocytes expressing high affinity for self antigen.[3] Incomplete clonal deletion results in apoptosis of most autoreactive B and T lymphocytes.[3] Complete clonal deletion can lead to opportunities for molecular mimicry, which has adverse effects for the host.[3] Therefore, incomplete clonal deletion allows for a balance between the host’s ability to recognize foreign antigens and self antigens.[3]
Methods of exploitation
Molecular mimicry
Clonal deletion provides an incentive for microorganisms to develop epitopes similar to proteins found within the host. Because most autoresponsive cells undergo clonal deletion, this allows microorganisms with epitopes similar to host antigen to escape recognition and detection by T and B lymphocytes.[3] However, if detected, this can lead to an autoimmune response because of the similarity of the epitopes on the microorganism and host antigen. Examples of this are seen in Streptococcus pyogenes and Borrelia burgdorferi.[3] It is possible, but uncommon for molecular mimicry to lead to an autoimmune disease.[3]
Superantigens
Superantigens are composed of viral or bacterial proteins and can hijack the clonal deletion process when expressed in the thymus because they resemble the T-cell receptor (TCR) interaction with self MHC/peptides.[1] Thus, through this process, superantigens can effectively prevent maturation of cognate T cells.
References
External links
- Clonal+deletion at the U.S. National Library of Medicine Medical Subject Headings (MeSH)