T Cell Positive Selection

• T cell recognition of self MHC molecules confirms T cells recognize host MHC molecules.
• The body selects immature T cells recognizing self MHC molecules on cortical epithelial cells in the thymus.
• This selection is vital for transitioning from innate to adaptive immunity.
• Failure of double positive thymocytes to bind to MHC or foreign antigen plus self MHC results in apoptosis.

Positive Selection

• Positive selection ensures only thymocytes that bind self MHC survive.
• It is the "first real exam" for thymocytes originating in bone marrow.
• Double negative thymocytes enter the subcaspular region of the thymus.
• Differentiation yields double positive thymocytes expressing CD4, CD8, and a TCR with CD3.
• Double positive thymocytes binding MHC class II receive a protective signal that prevents apoptosis and stops CD8 expression.
• These differentiate into single positive CD4 thymocytes.
• Double positive thymocytes binding MHC class I receive a protective signal and cease CD4 expression.
• They become single positive CD8 thymocytes.
• About 98% of thymocytes die via apoptosis in the thymus.
• The high death rate is due to eliminating thymocytes failing positive selection criteria.

Negative Selection

• Negative selection selects T cells with low affinity receptors for self-antigen.
• This is a checkpoint for self-tolerance, reducing autoimmunity.
• Thymocytes passing positive selection move to the medulla for negative selection.
• Thymocytes efficiently binding self peptides are potentially auto reactive and undergo apoptosis.
• Antigen presenting cells (APCs) like dendritic cells and macrophages in the cortical medullary junction present MHC class I or II with/without self peptides to single positive thymocytes.
• Thymocytes with high affinity receptors for self-antigen/MHC undergo apoptosis to ensure tolerance.

Importance of MHC Binding

• Thymocytes must bind with MHC complex proteins to function.
• CD8 cytotoxic T lymphocytes interact with MHC class I on infected cells.
• T helper cells interact with MHC class II on antigen presenting cells.
• T lymphocytes reacting with self undergo programmed cell death to prevent autoimmunity.
• Autoimmune disease can occur if MHC proteins do not effectively train T lymphocytes to recognize "self".

Thymocyte Populations and Gestation in Mice

• C3 is a marker for thymocytes.
• Delta/gamma T cells leave the thymus early in gestation without selection, providing innate immunity.
• Alpha/beta T cells undergo positive and negative selection, appearing later in gestation.
• Selection provides a subpopulation of helper T cells which transition immune response from innate to adaptive.
• They play a role in humoral and cellular immunity.
• Gamma/delta T cells are higher during early gestation.
• They are present in smaller quantities in adults compared to alpha/beta T cells.

Gamma/Delta T Cells

• They are prominent during early gestation and involved in early immune responses.
• Gamma/delta T cells play a role in protection from infections and tissue homeostasis.
• They are abundant in the fetal liver and thymus, moving to tissues/peripheral sites as gestation progresses.
• They are part of the innate immune system due to innate-like properties and a quick response.
• Gamma/delta T cells recognize stress signals/non-peptide antigens without adaptive immune activation.
• They produce cytokines and immune mediators upon recognizing stressed/infected cells.

Summary of Thymocyte Selection

• Alpha/beta lineage thymocytes undergo extensive selection.
• Double positive thymocytes undergo MHC restriction.
• Single positive thymocytes with high affinity receptors are eliminated for self-tolerance.
• Delta/gamma lineage exits the thymus without positive/negative selection.

T cell positive selection ensures that only thymocytes capable of binding to self MHC molecules survive, acting as a critical step in T cell maturation. This process occurs in the thymus, where double positive thymocytes are tested for their ability to bind MHC class I or II molecules. Successful binding leads to further differentiation into single positive CD4 or CD8 T cells.